In September, Mark Fendrick, MD, co-editor-in-chief of The American Journal of Managed Care, led a discussion of experts about advances in the treatment of metastatic melanoma, which examined both the promise offered by new therapies and the issues surrounding cost, payment, and delivery. The text of their discussion has been edited for clarity, style, and length. To hear the full discussion, please visit http://www.ajmc.com/ajmc-tv/panel-discussion. Joining Dr Fendrick were:

 senior member of the H. Lee Moffitt Cancer Center and director, Donald A. Adam Comprehensive Melanoma Research Center, Tampa, Florida.

of the Johnson Comprehensive Cancer Center, University of California, Los Angeles.

 manager and medical director of Oncology, Well-Point.

 To start, I’m going to call on you, Dr Weber. Why don’t we start with a therapeutic overview and perhaps a broader discussion of the unmet needs in our current therapeutic armamentarium?

 There has been a tremendous amount of progress in cancer therapeutics in the melanoma field in the last 5 years. Melanoma has gone from being regarded by many oncologists as an impossible to treat and hopeless malignancy to a disease that one would argue is the poster child for new targeted and immunologic therapies, so we’ve come a huge distance in the last 5 years, and it has been very gratifying. That being said, there are major unmet needs in our field because while we are achieving good response rates with targeted therapy, prolonging survival with immunologic therapies, we still have a pretty narrow repertoire of drugs to use and they still have pretty serious toxicities, and we are a long way from curing a significant proportion of our patients. So, to me, the biggest unmet need is understanding essentially how to cure patients, and I use the word “cure” in the sense of having someone adoptive cell therapy, an area that both Dr Ribas and I are interested in, trying to figure out how to bring that into the mainstream is very difficult, and how to overcome resistance to the targeted drugs, because a lot of patients get great response with these targeted personalized drugs that impact on the signaling pathways for melanoma growth and proliferation, but almost all of them will eventually progress. We are trying to figure out how to overcome the resistance.

 I fully agree with everything you said because having seen this remarkable change in a short period of time with agents that have come from understanding biology, the melanoma biology or the immune biology of melanoma, and leading to rational drug development and to this remarkable benefit to patients, it has been something that has invigorated all of us, but we are still faced when we go to the clinic with many patients who are either not responding, responding for a short time and progressing, or having side effects. But, the process has gone so rapidly and based on things that we can rationalize and understand, that your point of saying we are shooting for a home run, we are trying to get durable responses in the majority of patients, I don’t think it is an unrealistic goal anymore in melanoma, when it was a completely unrealistic goal 5 years ago. Having said that, I would move on to the next point of the agenda, which would be these recent successes, and, what do they mean? Dr Weber has already pointed to the general theme of targeted therapies giving an initial response rate that tends to not be durable, and the appropriate immunotherapies interleukin-2, aldesleukin, or ipilimumab that are good for blocking antibodies, giving a much lower frequency of responses, but clinically very significant for the patients who respond because they can go on to have years of response and probably be cured.

Patients who were treated 2 to 5 years ago, some of them by Dr Weber, continue to respond and patients with T24 blocking antibodies, the longest one is now going for 12 years, a patient in my clinic continues to respond and we just see each other once a year. So the goal is there, but we need to make it more efficient for everyone. The particular agents that we will discuss and try to understand the cost-benefit ratio would be the B-RAF inhibitors, vemurafenib being the first one, and then the B-RAF that is called dabrafenib, which is a very recent approval. These are agents that when we select patients with the B-RAF mutation, which is around 50% of melanomas, we are close to guaranteed to have some kind of patient benefit.

Over 80% of the patients have some shrinkage of disease at some point over time, and that is shown in impressive particle plots with these agents, but the majority— not all of them, but the majority&mdash;will progress within a matter of months usually, and the median duration of response is around 6 to 7 months, although there are some patients from the Phase I trial of vemurafenib who are now going beyond 4 years and are continuing to respond, but that is the minority.

The benefit to patients is very rapid. These are targeted therapies that block the driver oncogene, which leads to cell cycle arrest and responses in the majority of patients, but then the majority of patients will progress. Around two-thirds of the progression mechanisms go through reactivation of the same pathway and a signal through an immediate downstream, a factor which is called MEK, which is a kinase under BRAF and them we have the MEK inhibitor trametinib that has been approved to use a single agent in B-RAF mutant melanoma. But that is not where we are going to be using it because by itself, trametinib is less effective in mutant melanoma and more toxic, so it is probably one of the only approvals by the FDA that we know from the start that we are not going to be using it the way the current label is written. You can use it in combination with the B-RAF inhibitor and you can use it in patients who progress on the B-RAF inhibitor because there is actually no activity there. But there is a lot of activity when you put it together, and that is something that Dr Weber has reported on, where it is one of the first examples that I would know in medicine where you have 2 effective drugs, that you put them together and they are not only more effective but they are less toxic when you keep them together, which should impact on the cost-benefit ratio because even though obviously 2 drugs are more expensive than 1, the side effects decrease and the benefits of the drugs is markedly improved and randomized trials are still ongoing, and that is why it is not in the label. It would suggest to me that in the near future I think most of us will agree that this will be a drug that is cost-effective.

 I think everyone agrees with that, and I think the expectation certainly is that the Phase II study results … with those 2 drugs are going to show serious benefit and major prolongation of survival, but again we don’t have the data and they won’t be out probably for another year, but maybe circling back to the issue of the immunotherapy agents, I think everybody is impressed that both the PD-1 antibodies from BMS and Merck, those are nivolumab and lambrolizumab … and the drug which doesn’t have a real name, it is MPDL from Genentech which is a PLD-1 blocking antibody  … everybody accepts that they have serious activity, good response rates in the realm of 30-plus-percent, and they appear to induce a significant number of long-term remissions; and whether they will overall prolong survival, that awaits the results of some ongoing Phase III studies, but they look awfully promising.

 The optimism and the advances are very impressive. I would like to—for some of our audiences, Dr Weber, can you just let us know a little bit about whether all of these agents are IV or some of them orals like we’ve seen with biologics, and also comment just a little bit on frequency if there is any differentiation. Many of our audiences have seen, in other classes, great emergency of multiple agents, some of which are very similar, some of which work together, and are very, very intrigued, but we will talk about this later, about the combinations, because any time where the situations is where the sum is greater than the parts, as Dr Ribas alluded to and you confirmed, that is something always of great interest, not only to our clinicians but also to the folks on the managerial side.

 The nice thing is that dabrafenib,trametinib, vemurafenib, and a lot of these drugs that are being developed are all oral, you take them once or twice a day, it makes it very easy for the doctor and for the patient, whereas interestingly virtually all of the immunologic agents that are in development are given intravenously. Ipilimumab, for example, is given every 3 weeks and to be honest, with ipilimumab, we haven’t settled on the optimal dose. There is a big trial of the standard approved dose of the 3 mg per kilogram given intravenously every 3 weeks versus 10. Ten may be better, and we will talk later about what implications that might have for the cost because it is not a cheap drug, and if it turns out that the FDA will now approve 10 instead of 3 (mg), are they going to triple the price? Nivolumab and lambrolizumab are given every 2 weeks.

Sometimes lambrolizumab is every 3 weeks, which it is not clear ultimately how often that will be given, but we are talking every 2 to 3 weeks in the veins which is not hugely convenient for the patient, but that is the way these drugs seem to have been effective, and it looks like the PD-1 blocking drugs or the PLD-1 drugs will have great promise; they are in Phase III studies.

I am optimistic that we will see positive outcomes. I should add that the excitement at ASCO was all about these drugs. Dr Ribas gave a great talk at this session, at the ASCO meeting in June in Chicago. I then gave another talk. I think that is where all the excitement was, and probably they saved the best for last because there was a combination trial of one of the PD-1 drugs nivolumab with the CTLA-4 blocking drug ipilimumab, and there someone commented that the waterfall plot, where you see in a graph the bars up or down indicating shrinkage or growth, looked like it was a targeted drug, it was so good. Toxicity, on the other hand, was not so trivial but that combination looked awfully impressive. Now, not only are we thinking about how do you combine the targeted drug, now you think about how to combine the immunologic drugs, so that is 5 more years of work at least to work that out, and that will be impressive.

Are most individuals now just getting orals, or are there individuals just getting IVs? Obviously you can imagine there is a strong preference from a patient perspective to avoid getting into the veins, as you say, Dr Weber.

 I certainly would want to hear from Dr Ribas and others, but the key question that will be addressed in one of the world’s most complicated trials is, what is the best sequence of a targeted drug and an immunologic drug, and it is not just a (single) drug, it is what combination of targeted drugs and what combination of immunologic drugs, what should be the proper sequence? Should you give the targeted drug first, should you give the immunologic drug first? That actually isn’t just a major unmet need; that is a major unanswered question, and I think Dr Ribas is involved heavily through these cooperative groups trying to answer those questions, so I will defer to him.

 About the mode of therapy and the benefits, it is moving so fast, we are in situations where we have no data about how to recommend patients with the B-RAF mutant melanoma; should we start with a single agent or hopefully a or PDL-1 and hopefully in combination with ipilimumab? The delivery of the agent is based on what they are targeting, so the B-RAF and MEK inhibitors need to permeate the cells and block enzymatic function, so those are the small molecules and those are formulated as pill drugs because they can go through membranes. As a small molecule, they can get inside the cells as opposed to the immunotherapeutics, which are blocking negative regulatory pathways of the immune system. This is a concept that came about first with Tim Allison’s description of anti-tumor activity of CTLA-4 blocking antibodies, on which ipilimumab is based. What we are trying to do is get the immune system to attack the tumor, and the tumor is growing from inside and the immune system doesn’t recognize that as something bad, and it has breaks that are built by nature to avoid cell reactivity to normal tissues, and as we take a break like CTLA-4 we get some patients to respond. Within another more relevant break, PD-1 and PDL-1 interactions, which is a break when the immune system cells are ready to attack the tumor in the final stage of an immune response to cancer. We take that out, and now we have higher responses, less side effects, and hopefully they will demonstrate to be durable responses. Those breaks are surface proteins, and those surface proteins have no instamatic activity by themselves, so they are blocked by specific antibodies that are blocking antibodies to the receptor. That is why they have to be given intravenously.

: That is very helpful. I am going to ask our clinician experts 1 broader question, and I’m going to tee you up, Dr Malin. With all this activity going on, and all of this enthusiasm and trials in place, how do payers actually assess value and ultimately determine access to these agents? The question I would like to ask is, I was involved in a medicine panel that released a report yesterday on geographic variation in healthcare delivery, particularly showing a variation tends to be greatest when even the experts in the field don’t know what the right path is for a particular condition. We have a faculty member from Southern California and one from Northern California, but you are obviously engaged nationally and internationally. What can you say about a standard of care, or a lack thereof in metastatic melanoma, given all of this exciting innovation going on in the field? Is it the wild, wild west, or are there guidelines similar to what we used to see from the National Comprehensive Cancer Network?

: Well, there are NCCN guidelines for metastatic melanoma, and a lot of private practice doctors in South Florida where I practice in our academic center will follow them. In fact, they will write it into the notes. Dr Ribas and Dr Malin, I assume in your area that is the same, isn’t it?

 I think NCCN has done a tremendous service to the field of oncology in that we do have very comprehensive guidelines, and they are updated very frequently. This is very helpful in an exciting area like melanoma, where there is so much innovation and so many new therapies that there are not hard data on how to sequence them, so you really have to rely on experts to provide that kind of guidance to people out there in the community treating patients. I will say, however, that before this call, I checked how NCCN was recommending use of the 2 new B-RAF inhibitors and they were FDA approved in May, and NCCN hasn’t updated its guideline. So, there is a little bit of a lag, and I think it is challenging. It is a good challenge to have, so many new therapies all at once that you are not sure yet how to choose among them and how to sequence them. I think we will see over the short period, as we are all struggling to figure this out, a lot of heterogeneity in practice, and I think that is understandable.

Also, I think practices will vastly vary at an academic center like mine where you have 25 melanoma trials. At UCLA I’m sure it’s the same. It is going to be a little different than if you are in Albuquerque, New Mexico, at a good private practice with 5 other oncologists. It is going to be very, very different as to what you can offer the patient.

 Right. Maybe this brings up the issue of access. These therapies are very, very exciting and the benefits that some patients have are really tremendous. It is very exciting to see someone go into a complete remission following 4 treatments of ipilimumab and stay in remission even for a year, which wouldn’t have happened before. But, the wholesale cost of just the drug for that is $120,000, combination of B-RAF inhibitors, or start with immunotherapy, hopefully a PD-1 so most private practices, most small, independent practices (are) concerned about even taking on the financial risk of a drug that is that expensive without knowing whether the patient’s insurance is going to cover it, whether the patient can afford whatever their copay might be. If they have a 10% copay, that is $12,000 right there, so the cost of these drugs, at least in combining them, is going to bring new questions regarding access for people. We’ve seen this recently with CML where CML is the 1 disease that I think the treatment has transformed since I was in training with Dr Ribas, and these drugs really are unbelievablein terms of the dramatic change in terms of the impact of the disease on people’s lives. They really do live in symbiosis with their disease for probably, it appears now, to “what their natural life expectancy would be.” But the drugs cost over $100,000 a year. Even some of the original ones like imatinib, the price has been going up each year quite steadily. So much so that recently there was an editorial in 

, signed by a large number of the hematologists that treat these patients, that the crime is profiteering. I think if we are looking at imatinib in combination with another drug, an anti-PD-1 drug, we don’t know what the price is going to be of those other therapies, but it is easy to envision that we would be looking at several hundred thousand dollars a year of therapy, and a therapy that someone might get retreated with.

People can have long remissions and some people do benefit from retreatments so we don’t know, to achieve that vision of 10 or 15 years of symbiosis, does it mean someone is going to need to repeat treatment every couple of years? I was mentioning earlier that many independent practices feel that it is too costly, but when someone gets the treatment in an outpatient hospital setting, usually the cost is double or triple, so just for ipilimumab, we are looking at a cost to the patient’s payer, which eventually is actually their employer, of $240,000, $360,000. That is really what the true cost of the therapy ends up being after whatever the markup is from the hospital. The price of these we need to be very conscious of to insure that people have access to these therapies.

 I think this is something that is at the top of everybody’s consciousness in the medical field. There are a number of things that will come into effect over the next few years, in that the NCI, the FDA, just about every professional group is going to emphasize the idea of trying to have biomarkers to select the right patients. You can’t just treat 100 patients and benefit 8 of them. It is not going to happen in the future, and the FDA has made it very clear how important they think biomarkers are. The classic was the B-RAF mutation test that was approved when they approved dabrafenib, so the 2 variables will be selecting the patients more appropriately, and determining what the value will be. I predict that you are not going to get the (Oncologic Drugs Advisory Committee) and the FDA to approve drugs or push forward unless there is clear, significant value; a 5-week prolongation of survival is not going to cut it in the next 10 to 20 years, not when the drug costs $120,000 just for the wholesale price. As Dr Malin just pointed out, you increase the price because you have to add the margin of profit for the hospital, you have to add the nursing costs, the infusion cost, the doctor cost, etc, so those 2 driving forces will help, and the final thing is, there is only so much money in the world and certainly there is only so much money in this country.

At the current rate, I suspect if you graph the price of current drugs over the last 20 years, you would see at least a linear increase with a doubling every 5 years and eventually what is it going to be, $300,000, $400,000, $500,000, or $600,000 to treat someone? That is just not practical. There will be pushback from citizens, there will be pushback from every walk of American life. People study this, and Dr Ribas probably knows these data and can correct me if I get it wrong, but Tom Smith, who used to be at the Medical College of Virginia and is now at Hopkins, studies what Americans think would be a proper amount of money to spend per year of life...the so-called marginal value of a drug, and it is not $500,000, it is not $20,000, it is somewhere between $50,000 and $180,000, and that is kind of where ipilimumab is and vemurafenib is. You are adding, and looking at the dabrafenib, trametinib price together, and if you add it together and multiply that by the profit margin and then you add that it is a monthly charge over a year or 2 years, it is $200,000 a year. I just think people won’t accept it, and I think the companies are going to have to cut the price. I’m not an economist, but I find it hard to believe that for them to stay in business they need to charge $200,000 a year for dabrafenib and trametinib.

 Dr Weber, we don’t have anyone representing the manufacturers’ side on the line, but you are falling into my own area of expertise and all of the numbers you say are, of course, right on, except it is not talking about who is actually paying, the employer or the government through organizations like WellPoint that are paying these dollars.

You and I are paying. It is our tax dollars that are going for this.

: I wanted to ask a question, an easy one, and then comment on some areas where 

 has taken the lead. Dr Ribas and Dr Weber, I would like you to comment on whether you actually feel there is cost-related nonadherence and lack of access right now, and I just want  to throw out very quickly the concept that the other co-editor of

, Mike Chernew, and I developed over 10 years ago called value-based insurance design, and you should at least find some solace to know that one of the slowest areas of healthcare cost growth in the United States is pharmaceuticals overall, largely because of the emergence of generics in the small molecule market, and everyone is focusing, of course, on you guys in the specialty pharma area where almost every American who has coverage, and especially in pharma, pays an equal amount of coinsurance on every drug. That being a drug that cures cancer like the ones you are talking about, as well as ones that hardly work at all, or even best case scenario, prolong life by just a few months, so we have proposed with great support from ASCO, NCCN, and COA and everyone else, an idea to extend value-based insurance design to especially pharma, where coinsurance would go much lower for the drugs that work as well as you say, particularly in the case of metastatic melanoma, and cost sharing would go up when you use agencies that are off label or for rescue therapy, and this is being discussed by multiple stakeholders that are used in other areas of medicine now, but now just being explored in, especially, pharma. Imagine that a combination is discovered that works all the time, regardless of the manufacturer’s price, the cost to the patient would be lower than for a combination of agents that you would never, ever use but see being used out there by people behind the curve. With that editorial comment, what do you see happening now regarding cost-related lack of access or nonadherence, if at all?

: It is certainly happening for ipilimumab. In places like the county hospital, it is hard to find any patient who has been on ipilimumab because it has not been approved for administration even though it is an FDA-approved drug and there are randomized trials that demonstrated approval and survival. Those randomized trials showed improvement that is based on a small percentage of patients, around 10% to 15% when we look at the totality of the difference between the control curve and the ipilimumab curve, but to try to make a point in favor of the manufacturers of these drugs, especially BMS for ipilimumab, ipilimumab took 10 years of clinical development and several thousand patients treated until this benefit was demonstrated in randomized trials. Why would it take so long? Because, as Dr Weber was saying, we don’t have a marker and possibly we will not have a marker because it is an agent that is activating the immune system very far away from the tumor, so there are several thousand genes that are involved from the activation, from the release of CTLA-4 and until a T-cell kills the tumor and shrinks the tumor. So it is unrealistic to think there is going to be 1 biomarker that says this works or doesn’t work in patients, or even in niches for responders and nonresponders. Both Dr Weber and I, in our labs, have dedicated over 5 years of research in these and we are back to where we were, which is we give it to everyone because we don’t want to miss those patients that can go on to have decades worth of life and continuing free of metastatic melanoma. Those are people that should not be alive but continue to be alive, and are going on with their lives. That is something that I have trouble putting a price on, but the worst case is when we don’t even have the chance to give it, and that is what is happening with the price of ipilimumab being so high, and as Dr Malin was saying, it is not only the wholesale price, it is the total bill that I see, and I am outraged every time a patient comes and says this is what your clinic charged my insurance to give 4 doses of ipilimumab.

 To further address the question, are there people for whom it is not available? We have had the occasional referral to Moffitt, a charity patient who has either Medicaid from another part of the state, like someone from Miami, who is a bit of a distance away, and actually the folks at the University of Miami will not treat them and have occasionally been referred here and Moffitt will either eat the cost of some percentage of those patients, or BMS will make the drug essentially available free, for example. Generally we have gotten along and I can’t think of anyone who has denied it, but it certainly can be a torturous process to get treated with the drug. A lot of the companies have these programs where if you can’t get anybody to pay for it, they will give you the drug for free, for either a huge discount or for nothing, so eventually it happens, but it can be a huge hassle for everyone concerned.

: We have seen this and tied in some very important points about biomarkers and targeted therapy, and there is practically zero cost-related nonadherence to Herceptin and HER2-positive patients just because of the compelling evidence for them, and I’m hoping not knowing your field anywhere near as well, that what you say Dr Weber is happening at Moffitt in Tampa, will expand around the country.

Dr Ribas, is that the case at UCLA? I guess UCLA is a state hospital and they take Medi-Cal and they have charity patients, and I assume everyone eventually, in spite of the hassles, who merits getting treated with ipi will eventually get it, is that correct?

Yes, there are patients who don’t get to our clinics, and other patients who have no insurance at all that aren’t seen at the county hospital, which is normally where you see patients. ....when I talk with the doctors there, they tell me that it is very seldom we are able to give ipilimumab to a patient because of the cost.

I can see that being an issue for the poorest patients. Those who are at the LA County Hospital, I can see that being a big issue, because I’m not sure what Medi-Cal does, whether they will cover the cost of the ipilimumab. That is a good question. But, it is a huge debate. Again, this was a huge topic of conversation at this Advisory Board I recently attended at ASCO on this very topic, and I can’t go into the exact details of what drug we were talking about, but the question was, what if the price were $300,000 or $400,000 to get treated with some regimen lasting a year, would that be realistic? My opinion was, there is only so much money in the United States. You are going to run out of money and you have to cap the cost, and where that cap goes is a national debate or dialogue, but I think our scientists who study this will tell us that Americans will accept somewhere between $100,000 and $200,000 expended on this kind of treatment for a year’s worth of treatment that will seriously prolong your life.

 Again, it matters if it is their money. You don’t need to cap the cost, you need to cap the coverage and I think there will always be people with resources willing to spend unlimited amounts of money on evidence-based and, unfortunately, non—evidence-based therapies, and it is pervasive in this country. I would like to go back to Dr Malin for a second and you said something, that many of the managed care pharmacists that we touch on a regular case basis may take an argument with you on the fact that you said how exciting it was to have a large number of innovative, expensive therapies that we don’t really have a full dossier of evidence on. The kind of thing that really makes managed care pharmacists crazy is the fact that they are pushed harder, and harder, and harder to identify preferred agents, much more so out of the cancer realm, but more and more in the cancer realm. I wanted you to comment. There are many reports in 

on new models of payment in oncology, particularly a bundled payment or an episodebased payment for a condition over a very long period of time, as opposed to the a la carte approach that we have been talking about a lot on this call, and you can imagine when you are capitated or bundled, or episode group or whatever the term is, there is at least a theoretical perception that people would not use the best, if expensive, agent, and instead start with lower-cost agents, which is something we are very accustomed to in the small molecule world.

 In the oncology world, there have been a number of folks who have talked about episode-based payments and a proposal of those models. Dr Peter Bach at Memorial Sloan-Kettering has written extensively about it, and I think while conceptually it is appealing, it is very challenging to implement in oncology for a number of reasons. First of all, depending on the disease characteristics and biomarkers that the patient has, the cost of treatment may be $10,000 or $300,000, and so unless you have incredibly large risk pools, how do you account for the fact that just the natural prevalence of those things is going to vary? Then you have this rapid innovation, so how do you adjust the episode payment for when a new drug gets approved that costs an extra $100,000?

Then there is the fact that just the way our system is designed, some drugs are paid for under the medical side, and some drugs on the pharmacy side. Envision how would you construct an episode payment for melanoma when you have ipilimumab that let’s say, just the average sales price is $120,000, but all the Bâ€‘RAF inhibitors would be covered under the patient’s pharmacy benefit. Do you say that the practice has to pay for those oral drugs as well out of their episode payment and they have to provide it whether it is IV or oral, which impact or benefit design then? It is very, very complex to try to envision how you would come up with a single payment for an episode, and not have a thousand different types of episodes in order to capture the heterogeneity of these diseases and the cost. A global capitation has certainly been tried and there are some large medical groups that have capitation more globally with stop/loss ratios in California, but again, there aren’t really good data for us to know whether access to innovative therapies is impaired in those kinds of environments, and we have seen some concerning signs regarding use of counterfeit drugs and things like that, in environments where practices are more pressured financially. The approach we are favoring at Well-Point is a pathways approach where we are in the process currently of designing a pathways program and our goal there is to insure that there is parity between more cost-effective treatment options and the higher-cost treatment options to the practice that is treating the patients. One of the vague ways that we reimburse oncology is that most of the revenue for a practice comes from the margin on the drug they prescribe, if you are talking about independent practices and certainly hospitals as well, although the treating physicians and the hospitals may have a less line of sight into that, so if you are looking at 6% of 5FU, that is 17 cents margin. If you are looking at 6% of Herceptin or ipilimumab, Herceptin, the average cost for treatment is probably around $3000 and that is a big difference from 17 cents for 5FU margin when you are talking under $60, and 6% of ipilimumab if you feel you want to undertake the risk of not getting paid. The current reimbursement system really provides no incentive for physicians to select the most cost-effective therapy even if the treatments are equally effective, and so the idea behind a pathways program is you have a group of experts who review the regimens, review the NCCN guidelines, and if there are treatments that are equally effective for a given patient type, then you would have on your pathway the least  effective of those treatments and then provide additional funding for the practice so that they stay whole if they are choosing the most effective and most cost-effective treatments.

As we heard in Dr Weber’s complete introduction, oftentimes we don’t have the answers when we have to make decisions on this issue, but you have articulated, almost in an academic way, the imitation of the bundle payment model. Although these have been discussed for quite some time, it is our impression from the AJMC standpoint that it hasn’t slowed the momentum to see these things moving forward, so limitations notwithstanding, I think these are things that you folks in practice are going to have to deal with head-on. I want to ask 1 last general question of the 3 of you, and just to make a point that may make Dr Weber feel better, this week Governor Jack Markel of Delaware signed a bill limiting patients’ out-of-pocket expenditures for specialty drugs to $150 a month. So you can imagine if these bills go forward (in other states) and we end up pushing the other side of the cost of these agents into premiums and other types of things, it will have certainly a much, much different effect than if patients had to continue to pay 10% or 20% coinsurance every time they got these things prescribed. So there at least is some movement on the state policy front, and some initiatives are actually happening on Capitol Hill as well, to actually see copay relief for specialty drugs, at least with some evidence-based requirements as Dr Malin outlined. I want to ask 1 thing that comes up a lot also for our readers—the issue of Sterigen’s Center of Excellence, and what you thought about the idea of a situation where patients would get better coverage or lower cost-sharing if they went to Centers of Excellence for specific types of cancers? Just theoretically say that the Johnson Center and the Adams Center were designated as Centers of Excellence by payer organizations like Dr Malin’s. Do you think it is a good idea or a bad idea for particularly rare cancers to follow a model that we’ve had in place for transplants for decades?

I guess as long as it is legal, I wouldn’t have a problem with seeing more patients and bringing more business to places that excel at what they do. To be honest, if I had a metastatic melanoma and I were living in some rural location in a large state geographically isolated from the large center, I would probably go to the big center, no question.

You would favor benefit designs encouraging that?

That is an interesting question. My first query, is that actually legal? Can you actually, financially penalize someone for where they choose to get their treatments?

You are not penalized. Just so you know, Dr Weber, the Cleveland clinic, for instance, has multiple contracts with multiple large employers for employers around the country to send their patients to Cleveland, which I call negative medical tourism, for their cardiovascular procedures, so I’m not suggesting that they raise cost sharing to go to certain places but to lower it for others, and I’ll just say, and Dr Malin certainly knows, this has been the core contract behind networks and health insurance products for at least 4 decades. Dr Weber, you probably have a health contract with lower costs for you to go to certain doctors as opposed to others.

 I know these exist, these types of products exist, so I would not spend a lot of time on that. I just want to get your impressions and opinion on evidence-based steerage.

 I think that Dr Ribas and I would probably love the idea, and we would welcome having melanoma patients all go to a specialty center, at least for consultation. Dr Ribas, I assume you would agree?

 I would agree. Sometimes we see patients on a second opinion coming from the community. The data the community doctor has are the same as we have, the drugs are the same but the usage may be wrong because they are not thinking about melanoma every day. My thinking is always that regardless of the cost, if we treat, it is cheaper than if we don’t treat. I mean treat, not just delivery of a nature, but we actually treat a medical condition and the medical condition improves. That is always going to be cheaper, regardless of the price of the drug, not an absolute, but we don’t give drugs that don’t work or give them in the wrong way...

There may be a value in having a centralized guidance of treatment adapted to a particular patient. We have NCCN guidelines, but that has to be interpreted for individual patients and that requires a clinic visit. With all of this discussion I just wanted to bring up 1 thing which is, even though things have come so rapidly, Dr Weber and I know it is going to change even further, that the PD-1, PDL-1 antibodies are going to change in the treatment of melanoma again within the next 2 years, and none of the price structure that we may be discussing now, it is going to be a problem for just a couple of years because the PD-1, PDL-1 antibodies, if we look at the data right now, suggest that we will get a significant fraction of patients with metastatic melanoma to have durable responses with therapies that are basically non-toxic or serious side effects that need to be intervened and will leave the patient in the hospital. It is basically non-existing, now that we know we have to anticipate what it is. There are 7 of those PD-1, PDL-1 antibodies in the clinic being developed right now, and probably there are going to be more that will be developed. There are 3 of them that are positioned to have licensing potential in melanoma and maybe many other cancers. I would assume that would drive down the cost, and instead of going the path of ipilimumab where it was to the maximum that it could, there was no competition, not a second CTLA-4 because the Pfizer one was negative and the trametinib, the clinical trial was negative for a whole bunch of reasons, and then there was not a similar agent besides high-dose IL-2 that could give durable responses in melanoma, but high-dose IL-2 would assume it is even more expensive than giving ipilimumab, so the field backing will go into what we are talking about which is adapting the prices to the benefit because there will be more competition and the existing drugs will become second-line drugs, and companies will not be able to be charging as much anymore.

 I think Dr Ribas raised a very interesting point. The essence of the capitalist system is that competition brings down the price for the consumer, and if you have 3 PD-1 or PDL-1 antibodies, how are you going to choose? If they seem equally effective, obviously whoever cuts the price the most, that is the one that is going to get used, and here you have in front of you an example, what is the price per month of dabrafenib, a drug that arguably is equally effective as vemurafenib, and has a slightly different toxicity profile that may or may not be superior. Its price is significantly less than debrafenib’s, and does anyone think that is an accident? I don’t think so. One of the solutions to the problem is as companies develop competing drugs, the price will to some degree come down, and look who is developing B-RAF met combinations, 3 companies, Novartis, Genetech, and GSK. The same thing is going to happen, it is not going to be $16,000 a month because someone will come in with a new approval and it will be $13,000 a month, and the next one will be $10,000 a month, so perhaps there is some relief on the horizon in terms of pricing because of competition, the classic essence of capitalism.

 The relief for price will fall only if the drugs remain equally effective. Evidence over 50 years would suggest that the prices will go up in toto as opposed to likely going down per agent, but I did want to let Dr Malin comment on this. What I find most interesting and learned a lot about over this session is that from a scientific and clinical outcomes perspective, the field of metastatic melanoma can be held out as exemplary in terms of innovation and science, and actually lead to better outcomes for individuals with this 1-time, nearly always fatal disease as you said, Dr Weber, so clearly that glass is half full, if not more than half full regarding where we are going on the health outcome side. Dr Malin, in terms of cost, are we half full or half empty, given the pressures that Dr Weber and Dr Ribas mentioned clearly on not only individual patients, but the healthcare system as a whole?

 I think clearly the cost of these new therapies is a challenge, just as the overall cost of healthcare is a major challenge for our country. There was a recent article in the 

 that was looking at the rate of rise of healthcare premiums and out-of-pocket costs, and in just a few years basically the cost that both the employer and the individual pay for their health insurance, along with their out-of-pocket costs, will be equal to half of the median family income. So clearly it is not conceivable that costs can continue to go up. We can not spend really more than we already are of our incomes on our healthcare, so as we get new, innovative therapies that are more and more expensive, in order to pay for them, it means that the dollars have to come from somewhere else in the healthcare system. Now the good news is we think that 30% of what we spend on healthcare is waste, so if we can figure out how to stop doing the things that don’t help people, we can insure that we can continue to make sure to make new therapies that are highly innovative available to people, but figuring out where that waste is, and getting people to stop doing things that don’t provide value is challenging, and I think you know the comments made about the costs will come down, the costs will come down likely if we can exert pressure like formularies.

Articles

Evidence-Based Oncology

Melanoma: From Impossible to Treat to Poster Child for Targeted Therapies

Increasing financial and administrative pressures—made worse by the federal sequester and continued rollout of the 2010 Affordable Care Act (ACA)&mdash;have created instability and uncertainty for oncology practices nationwide. To better understand how oncology practices are adapting to these stressors, the American Society of Clinical Oncology (ASCO) launched the National Census of Oncology Practices to collect practice-level data on the organizational, staffing, and service changes of oncology practices across the United States.

For an expert interpretation of the census data and its impact on independent oncology practices, we discussed the current state of oncology practice with Anupama Kurup Acheson, MD, medical oncologist at Providence Cancer Center Oncology and Hematology Care Clinic and 2013-2014 Chair of the ASCO Clinical Practice Committee. Acheson’s expert analysis covers practice trends, cost pressures, sequestration, healthcare reform, consolidation, genetic testing, new care delivery models, payment reform, accelerated drug approvals, clinical trials, and quality and value measures.

What are the principal cost pressures affecting independent oncology practices?

Reimbursement for patient care from Medicare poses a major challenge, especially as the medications and technologies we use are big-ticket items. The system has not been able to keep up with the upward cost curve. Also, with doctors facing the constant specter of severe cuts, the sustainable growth rate (SGR) formula represents an enormous impediment to successful healthcare delivery and payment reforms that can improve the quality of patient care while lowering growth in costs. The system is flawed and in need of a major overhaul, and it’s never been more important for oncologists to play a role in shaping the future of the payer system while also ensuring we are able to deliver high-quality, high-value care.

Another trend is that newer drugs typically cost a lot. Some specialty drugs, which are especially complex, also require management, particularly of toxicity. Different pharmacies offer varying levels of support, and so it’s very much part of our job to assist our patients while also helping them work out insurance coverage. This involves a major effort on the part of our office staff to accommodate payers, who request information in different ways; it’s not consistent.

Practices are also bearing the burden of the cost of some of these drugs. Chemotherapy drugs comprise the largest single expense for community oncology practices. These costs include purchasing the drugs, special storage and inventory costs, safe handling, and specialized staff to mix and administer the drugs as well as to monitor the patient during treatment. The federal sequester has also had a significant impact on the bottom line.

In a recent ASCO survey on the effects of sequestration, of the more than 500 practices that responded, 80% said they’d been impacted in some way. Fifty percent said they could not continue to care for Medicare patients without supplemental insurance, and about half said they were redirecting 10% to 50% of their patients to hospitals for chemotherapy. Around 14% said they were no longer taking Medicare patients.

What impact is the ACA having on independent oncology practices?

Under the ACA, physicians must participate in the Physician Quality Reporting System (PQRS) by 2015. The good news is that the Centers for Medicaid & Medicare Services (CMS) has released criteria criteria for the approval of existing, qualified registries as a reporting device under the PQRS. ASCO is working with CMS to ensure that our Quality Oncology Practice Initiative (QOPI) would meet these requirements. A major issue the law did not address is the SGR formula. This reimbursement formula is really flawed, especially in light of expected increases in costs and the aging of the population. Physicians would like to get away from the SGR, as it creates intense instability within oncology and the larger practice environment. We are aware that we will be seeing more patients under ACA, but we’re still waiting to see when and how the law will have an impact on practices.

What are recent trends in services that independent practices are providing, and what market or regulatory forces are driving these?

Last year, ASCO launched its first national oncology census to better understand these trends and found that just over 40% of practices were providing chemotherapy onsite, almost 30% were offering social services, and 23% nutritional counseling (see Figure). A quarter of practices had lab services onsite, and 26% were involved in clinical trials. The 2013 census is now open and we will be looking to its results for trend analysis. One aspect of practice we want to track is the increasing use of advanced practice providers (APPs), specifically nurse practitioners and physician assistants. In an ASCO study released in the fall of 2011, we learned that nonphysician nonphysician practitioners were seeing patients at office visits independently of physicians, although a physician was on hand. Notably, 98% of patients polled in one survey recognized that the provider they saw was not a physician, and the average satisfaction score (92.5%) indicated that they were extremely satisfied with their care from a team that involved physicians and APPs. Practices in which the APPs worked with all physicians were nearly 20% more productive than practices where APPs worked with select physicians. A 2007 ASCO workforce study also found that practices involving APPs have higher visit rates than those that do not.

Broadly, what we’ve all known is that beyond delivering chemotherapy, services such as counseling, nutritional guidance, and social services are all highlights of quality oncology care. Independent practitioners provide them in a range of ways—some smaller practices use outside providers, including hospital services, while larger practices have them onsite. But everyone feels these are essential. We need to stay tuned, however, to see what effects the sequester will have on these services.

What sort of consolidation are you seeing among practices? How are independent practices managing to go it alone and what are the implications for services provided

In the past 2 or 3 years we’ve been seeing a lot more consolidation as doctors transition out of community practice. One of the prime drivers of the recent census was to get a better handle on this trend, and from last year’s survey (http://bit.ly/asco_survey) we saw considerable movement. We’re seeing a lot of mergers, especially in metropolitan areas. Larger practices reported plans to purchase smaller ones, while smaller ones said they were more likely to close. Again, the sequester is having an impact. In order to survive in this environment, solo practices are paying close attention to information provided to them by community oncology consortiums on how practices across the country are coping. They are able to manage some costs by joining together;

group purchasing for drugs is an example.In terms of providing multidisciplinary care, independent practices recognize the value of interacting with specialty providers given the complexity of disease, and while this takes more time, they see it as a necessity. What sort of momentum is there behind new care delivery models such as patient-centered medical homes (PCMHs) and accountable care organizations (ACOs)?

Over the past few years, there has been a lot of talk about developing new models and growing calls for more pilot testing, with the understanding that these new models would require a wholesale change in how we practice medicine. In cancer care, however, it’s important to keep in mind that a onesize-fits-all approach will not work. ASCO would look for a menu of options:

different types of models that will support the level of care we need to provide. In the near-term, we’re looking for more pilot testing of clinical pathways to guide evidence-based care and patient-centered medical homes. However, we recognize that these models may make sense in some parts of the country and not in others. These pilots, which require a significant commitment of time and resources on the part of practices, are still in the early stages. But we are very encouraged. Going forward, we need to make sure the menu is developed thoughtfully and that we put in place a transition period so that we can fully assess how they are working. In general, oncologists must continue to tie the work they do to what’s important to patients. We need to be

more careful about utilization of tests and services, making sure that whatever we order is meaningful. A lot of positives will come out of this.

What’s happening on the payment reform front?

As the Medicare population grows, reimbursements for services are not keeping up with cost increases and we are bearing a large part of the added cost. So we are very encouraged at ASCO to see an appetite in Congress to reform unworkable aspects of the current payment system, including the SGR model and the fee-for-service system, which requires a wholesale change. Importantly, more elected representatives are reaching out to us for feedback, asking for our ideas about alternatives to SGR, for example. And we are putting pen to paper.

ASCO’s Payment Reform working group is examining proposals for different payment models. We’ve developed a set of principles, which we believe should underpin any new payment system. We believe any new payment system should be tied to quality improvement, be physician-led, not add to the deficit, and provide a transition period to allow for additional testing. The House Energy and Commerce Committee has asked ASCO to provide feedback on its draft legislation. We’ve been supportive of the legislative proposals that encourage all specialty physicians to participate in a quality assessment and clinical improvement program. Patient outcomes, with quality as the underlying goal, must drive these changes. To ensure value, physicians must make sure that the services we provide are clinically meaningful. The challenge is that there is so much variance among patients that care must be tailored accordingly. Also, these new models must work in relation to private payers; care has to be consistent across the patient population. But we do find that private insurers are interested in clinical pathways.

What is the impact on practices of new drug approval processes, including the FDA’s accelerated approval pathways? Are there increased responsibilities and risks as a result of these changes?

It’s very encouraging that the FDA is using regulatory flexibility to speed up the approval process for breakthrough therapies for life-threatening diseases. ASCO supports this and has worked closely, for example, with the agency’s Office of Hematology and Oncology Products to host workshops to advance surrogate end points for use in specific cancer types to enable use of the accelerated approval mechanism. In each case, how quickly these drugs are approved depends on the data and how easy they are to collect. The FDA has demonstrated the ability to approve agents on the basis of trials that involve a relatively small number of participants. This translates to earlier access to the agents, but this does place the responsibility on us as clinicians to closely monitor patients for unexpected side effects and on organizations like ASCO to advise our members that they may have to change treatment plans if there are adverse effects or drugs are not working. We also need to keep a close eye on information from clinical trials, understanding that use of agents in this setting is experimental, even if the agent is already approved for a different indication.  Particularly in the case of agents approved via the accelerated approval mechanism, the approval is granted on the basis of a surrogate end point that is reasonably likely to predict clinical benefit. We need to stay in touch with confirmatory studies and data from these trials to understand whether the agent meets the clinical benefit expectation.

Are independent oncologists enrolling their patients in clinical trials? What are the practice implications?

Independent oncologists are interested in enrolling their patients in clinical trials, and just over a quarter of practices say they are involved in them. But there are significant additional costs associated with conducting clinical trials, and the National Cancer Institute (NCI) doesn’t adequately reimburse for trials conducted through the Cooperative Group system. Changes the NCI and Cooperative Groups are implementing are helping to streamline the system and standardize the process, but the costs of conducting NCI-funded trials are not adequately compensated. This means practices lose money. In ASCO’s survey on the sequester, a quarter of practices polled said they  had stopped participating in them because of funding costs. Patients who are enrolled in trials need to be closely monitored, and nurses and other staff must take the time to counsel them. In addition, clinical trial participation involves staff with specialized expertise, increased data collection, facilities to store records and investigational agents, and time and space to accommodate auditors. On another note, ASCO is in the process of developing recommendations that will help design trials with more clinically meaningful outcomes. We are hoping that trial sponsors will use these recommendations to prioritize development of trials with outcomes that hold greater clinical benefit. In addition, another ASCO group is examining eligibility criteria with the goal of limiting exclusionary criteria that prevent patients from qualifying for trials. If eligibility is so stringent, it makes screening incredibly challenging and raises questions about how widely applicable a given treatment is down the road.

How are oncologists improving the quality and value of the care they provide, and how are they measuring their performance?

The QOPI is the first national program in oncology. It covers the spectrum of practice/diagnosis, treatment, and assessment—and a range of services, including psychological counseling and end-of-life care. QOPI includes 160 quality measures, including 26 core measures. There are 17 standards alone for safely administering chemotherapy. It’s a rigorous process, but it gives practices that participate detailed reports on how they’re performing compared with national averages. And it’s an excellent way to manage quality care and a valuable learning tool. To date, 850 practices are registered with QOPI and 180 have gone through the process and received certification. On the quality front, ASCO has just launched a prototype health information computer network called CancerLinQ that will collect and analyze individualized patient data from millions of visits and provide practitioners clinical guidance for real-time personalized care. For example, by inputting tumor characteristics, the provider would receive recommendations on what personalized therapies to pursue based on expert guidelines. This is a new way to get doctors information they can use in real time. They can also explore the database, which includes data on patient characteristics, treatments, and outcomes from a variety of sources to identify real-world trends. The system will also provide feedback on the services performed based on QOPI quality measures.

What is the impact of genetic testing on both oncology practice and care?

Tests such as companion diagnostics, biomarker tests, and next-generation sequencing allow us to provide more personalized care. These tests hold incredible promise to help us deliver molecularly targeted agents to the appropriate patient population, particularly with next-gen sequencing tests; however, they are not always available to community-based oncologists, and also may not be eligible for insurance coverage. We also need to be mindful of clinical utility. Some tests and use of molecularly targeted agents are of questionable applicability. It’s important to be clear about tests and procedures that provide meaningful clinical information to direct choice of treatment. We are in an era of rapidly expanding knowledge of the molecular basis of cancer, and it is important that we are clear about the difference between research, emerging data, and evidencebased care, so that we accurately present risk and benefit information to patients. As part of the American Board of Internal Medicine’s “Choosing Wisely” campaign, ASCO developed a “Top 5” list of procedures and tests whose use should be questioned. More generally, everyone looks to genetic testing for simple answers, but they are not always available. Just because we know A, B, C, and even D about a patient, there maybe other factors driving their cancer, including environmental inputs. Going forward, this is another area where CancerLinQ should shed some light as we are able to aggregate data quickly on treatment outcomes in the larger population of cancer patients.

Challenges in Oncology Practice

Just 3 governors made the Modern Healthcare Top 100 list for 2013, and Louisiana’s Bobby Jindal was among them.

 Jindal was included among the most influential weeks before the start of open enrollment under the Affordable Care Act, which featured elements he refused to roll out in his state. Louisiana would not have its own exchange to sign up enrollees, nor would it expand Medicaid.

That second decision has drawn loud and sustained criticism, given Louisiana’s history of poverty, health disparities, and cancer, much of it linked to oil and chemical interests along the Mississippi River. The corridor between Baton Rouge and New Orleans has long been called “cancer alley,” with many researchers noting the proximity of toxic emissions and cancer clusters among the poor.

Jindal didn’t just opt out of Obamaacare. He crusaded against it, writing op-eds in national publications. As an alternative, he designed a path of privatization to deliver care to the poor, one that retains some elements of Louisiana’s famous two-tiered hospital system while shedding others. Before Jindal’s trusted health and hospitals secretary, Bruce Greenstein, resigned following a scandal, the two brought privatization and managed care elements to Medicaid as well.

While privatization has both fans and critics—it has already resulted in the Louisiana State University hospital system laying off more than 1500 employees

— the bigger tumult came over Jindal’s denial of Medicaid to at least 214,000 Louisianans who might be eligible under the ACA.

 What outrages critics is Jindal’s perceived departure from his original plan, “Louisiana Health First,” unveiled in November 2008.

That blueprint, which came as Louisiana crawled back from Hurricane Katrina, called for expanding Medicaid to more caretakers of eligible children, or at least more additional low-income persons with chronic conditions.

 Offering the poor healthcare choices and providing preventive care at medical homes were seen not as dreams but possibilities, given Jindal’s expertise as a state and federal health official.

As Jindal built a modern academic medical center to replace New Orleans’ battered Charity Hospital, it seemed he would build a healthcare delivery system to match. The announcement came as 4 institutions—Ochsner Health System, and Tulane, Xavier and LSU&mdash; began to show the fruits of investing tobacco tax dollars on the LouisianaCancer Research Consortium (LCRC).

Among its goals, the consortium seeks better screening and earlier diagnosis, to combat a phenomenon common among the poor: cancer mortality is worse than cancer incidence, because too often patients are not seen until their disease has progressed beyond a point where it can be treated effectively.

• In 2011, approximately 22,780 new cancer cases were diagnosed in Louisiana, excluding some skin cancers and carcinomas.

• About 8360 people living in Louisiana died from cancer during 2011.

• Although cancer mortality is improving, rates in Louisiana remain about 30% higher than the rest of the country.

Beyond the political and media uproar, some amazing things are happening in cancer care in Louisiana. The growth of the New Orleans—based Ochsner Health System, its relationships with the state’s medical schools, and its decision to take over struggling institutions has allowed personalized medicine and cancer treatment pathways to take hold in places where change can

Ochsner, LSU, and Tulane collaborate through LCRC, and Ochsner is moving beyond treatment trials to preventive ones for breast and prostate cancer, 

 diseases that hit harder than normal here. So what’s the concern? While Jindal’s approach to upending Louisiana’s one-of-a-kind charity care system could spur even more collaboration, the failure to expand Medicaid means not everyone with cancer will get the same access, at least not now.

Over the past year, the big healthcare story in Louisiana has not involved cancer or the Affordable Care Act. It’s been about the transformation of Louisiana’s unique charity hospital system, which dates to 1736 and flourished under the populist governor Huey P. Long. Under Jindal, 9 of the state’s 10 charity institutions will convert from LSU management into public-private partnerships.

Five such partnerships are in place, with the remaining 4 set to begin in 2014. Proponents, led by Jindal, say the new system will reduce costs, improve care for patients, and offer better training for medical students. In an editorial published in July, Jindal claimed the partnerships were “on target” to save $125 million this year.

Certainly, there is much in Louisiana’s old system to be desired; an Institute of Medicine study released in August found 6 of the 10 highest cost cities for Medicare were in Louisiana.

 (Among the cost drivers was a need to shed retirement obligations for the thousands of public employees in the hospital system; Jindal stated that the changes would wring out $82 million in annual savings.)

For decades, critics of Louisiana’s charity hospital system asked whether the poor were best served with a system of healthcare segregation. The new arrangement does not fully dismantle the divide; the poor are still in separate facilities, but through partnerships these hospitals are now buttressed with private funding, management, and clinical expertise. Some critics predict private partners are biding their time and will absorb losses from the safety-net hospitals until Jindal leaves office, when Louisiana will expand Medicaid.

The partnerships are quite complex. Louisiana retains ownership of safety net hospital buildings, while the private partnership manages them and pay the state lease payments. In return, the private partners receive a share of Medicaid funds, starting with a guaranteed amount.

An interview with 2 top Ochsner physicians revealed the pluses and minuses of Jindal’s approach: Ochsner’s partnership with Leonard J. Chabert Hospital in Houma, Louisiana, gives that safety net hospital access to management and medical expertise it might otherwise lack. According to Ochsner Executive Vice President and Chief Medical Officer Joseph E. Bisordi, MD, FACP, Chabert is run just like any other hospital in Ochsner’s system. Thus, the partnerships can provide a different level of “access” for cancer patients who have coverage through Medicare or Medicaid. But therein lies the issue. For patients with incomes between Medicaid eligibility levels and 133% of the federal poverty line, “I am not sure we have an answer for those folks,” said John Cole, MD, who is Ochsner’s chair for hematology and oncology.

Steve Spires, health policy analyst for the Louisiana Budget Project, a nonpartisan research organization, said that the failure to expand Medicaid has longterm implications for the public-private partnerships, because state taxpayers will continue to experience the fallout of sick people overwhelming hospitals instead of seeking preventative care or catching cancer when it is treatable.

“The taxpayers will end up paying for this care,” Spires said. With cancer in particular, he said, “They will end up paying more than if we had paid for the preventive screening up front.”

The refusal to expand Medicaid frustrates those who have seen positive developments in healthcare over the past decade, including efforts to expand coverage for uninsured children and increase cancer screenings. A decade ago things seemed on the upswing, when Louisiana’s Legislature approved a tobacco tax to create the LCRC and seek a National Cancer Institute (NCI) designation within the state by promoting clinical trials.

Donna Williams, MPH, DrPH, has had a front-row seat for the decline in breast cancer mortality over the past decade.As director of Louisiana Cancer Control Programs for the LSU School of Public Health, she knows that early detection saves lives, because she has the data to prove it.

In 1995, the breast cancer screening rate in Louisiana for African American women was 59.1%, compared with a national average of 70.2%, putting Louisiana 48th among the states. LSU’s screening program launched in 2002, and data from the Centers for Disease Control and Prevention (CDC) revealed an immediate, steep drop in mortality among African American women, which later reversed somewhat after the massive population shifts following Hurricane Katrina.

By 2010, Williams said, Louisiana ranked 22nd among the states for 2-year mammography screening, with a rate of 76.3%, slightly higher than the national average of 75.2%. Louisiana screened 78.3% of African American women in 2010, compared with a national rate of 78.9%.10 Breast cancer mortality rates for all women remain well below 2002 levels, according to CDC data. (Figure 1.)

 But the good news with breast and cervical cancer is not repeated in other cancers, Williams said. Many whospoke with 

 decried Louisiana’s low eligibility levels for Medicaid, which typically leave the uninsured with long waits for care once cancer is diagnosed, assuming it is diagnosed in time.

As Williams and others explained, federal law requires Medicaid coverage once breast or cervical cancer is diagnosed. “They have fast-track qualification,” Williams said. “It’s a 2-pager; the providers attach the medical documentation and it goes through in less than 2 weeks.” By contrast, “If you have prostate cancer, you’re out of luck,” she said. “We don’t have any programs specific to the other cancers.” Much will depend on where a patient lives; those who use New Orleans’ current replacement for the defunct Charity Hospital fare comparatively well to those in remote areas, Williams said. Those familiar with the experiences of Louisiana’s uninsured say long waits and travel times can be as deadly as the cancer itself.

“People die as a consequence of this. That is not an exaggeration,” said Moriba Karamoko, director of the Louisiana Consumer Healthcare Coalition. “You can say people have access to oncology lists, but if the waiting list is so long and people die waiting, what kind of access do people really have?”

The Louisiana lifestyle, one that appreciates drinking, smoking, relaxing, and enjoying rich food (often fried), seems almost tailor-made to promote the kinds of cancers that are common in the state: lung, prostate, colorectal. Overlay an impoverished population, with demographics that tilt toward obesity, diabetes, and other risk factors associated with cancer, and it’s not a surprise that the state’s numbers are so high.

But another factor has been at work for decades: Louisiana’s relationship with industry. Because there are so many demographic and lifestyle factors in play, it has been impossible to prove that oil, gas, and chemical interests are responsible for even higher cancer incidence rates in certain areas of the state. The proximity of industry to cancer clusters in certain zip codes along the Mississippi, as well as western parishes like Cameron and Calcasieu, has long been noted.

Wilma Subra, a Louisiana native and winner of a MacArthur “genius” grant, gave up a career as a chemist for Gulf South Research 30 years ago. She founded a company to gather the science in support of residents who believed toxins from the plants near their homes were making them sick. She was able to document how the burning of toxic waste as fuel contributed to a spike in neuroblastomas in Amelia, Louisiana, and a judge ordered the facility closed.

that she has seen elevated levels of lung, brain, and organ cancers in areas where concentrations of polyvinyl chloride “are way over acceptable standards.” For years, she has worked with residents of Mossville, Louisiana, a community of mostly African Americans surrounded by chemical plants.

Subra says she’s no expert on healthcare policy, but the people she works with need more than they are getting. “We have a desperate need for medical care due to the toxic exposure,” she said. Young doctors rotate in and out, and they don’t always understand what they are seeing. She would like to see toxicologists on hand permanently; specialists are needed to treat the complex conditions that patients experience. But that requires money; either direct funding, or residents with Medicaid or health insurance.

“The community thinks there should be a free clinic,” Subra said. “But when you say ‘free’ industry goes beserk.”

For decades, if you lived in Louisiana, or on the Gulf Coast of Mississippi or Alabama, and your doctor said, “Cancer,” the next word was, “Ochsner.”

The renowned clinic was founded by Alton Ochsner MD, who was among the first to document the link between cancer and cigarette smoking; despite being criticized for this pronouncement, he opened the first group medical practice in New Orleans in 1942.

By fate of geography, Ochsner did not flood in 2005 during Hurricane Katrina and was able to stay open to serve residents after other hospitals went dark. Already a growing presence in Louisiana, it bought 3 hospitals in 2006,

cementing a strong “system” that Bisordi said will be key to delivery cancer care going forward. “One of the advantages we have as a system that you may not have as a small community hospital, you don’t have the structure to be more efficient. We have the resources in our system,” he said.

In addition, Ochsner enjoys good collaborative relationships with LSU and Tulane medical schools, which have programs to boost minority participation in clinical trials, Bisordi said. “Some of the patient samples from clinics at Ochsner go for analysis at LSU,” he said. Today, Bisordi and Cole say their goal is to keep patients as close to home as possible for cancer care. Ochsner does more clinical trials by far than any other cancer center in Louisiana—Bisordi said about 6% of the 2600 new cancer patients who come through its system participate in one. Yet not all come to the main hospital on Jefferson Highway, right outside New Orleans. “Our thinking with the community hospitals is, ‘We don’t want the folks you can take care of.’ Cole said, “care is best delivered closest to home.”

Cole said the Ochsner system is developing consistent, evidence-based pathways for cancer care delivery, which will be shared at the community level with all hospitals and clinics. This is the expressed goal of the Affordable Care Act—to promote cost savings by developing measurable methods to provide care, not by withholding it. If cancer care delivery improves, but a group of Louisianans lacks the means to receive it, what happens?

The Rev. Fred Kammer SJ, a Jesuit priest, Yale-educated lawyer and the former head of Catholic Charities USA now based at Loyola University New Orleans, has written about Medicaid expansion. He said that the discussion of the issue remains elevated among opinion leaders in the state. “It’s a scandal,” he said.

As the exchanges opened, Spires, of the Louisiana Budget Project, agreed. “Once people see the inequity, that people below the 133% of the poverty line get nothing, it’s going to turn up the heat. It’s by no means an issue that’s going to go away.”

1. 100 Most Influential People in Healthcare 2013. Modern Healthcare. August 24, 2013. http://www.modernhealthcare.com/gallery/20130824/PHOTO/824009999/PH&Params=Itemnr=70&Template=galleryzoom Accessed 0ctober 7, 2013.

2. Billings, FT. Cancer corridors and toxic terrors—is it safe to eat and drink? Trans Am Clin Climatol Assoc. 2005;116:115-125.

3. Jindal health secretary resigns amid investigation. March, 30, 2013. Associated Press, via Modern Healthcare. http://www.modernhealth care.com/article/20130330/INFO/303309964. Accessed October 7, 2013.

4. Selvam A. Louisiana’s health system sees massive layoffs. Modern Healthcare. July 18, 2013. http://www.modernhealthcare.com/article/20130718/blog/307189996 Accessed October 7, 2013.

5. Medicaid expansion could help thousands of uninsured Louisiana residents: Editorial. The Times-Picayune. September 15, 2013. http://www.nola.com/opinions/index.ssf/2013/09/medicaid_expansion_could_help.html Accessed October, 7, 2013. (Note: This editorial quotes a state projection of Medicaid expansion at 214,000. Estimates varied; some were in excess of 500,000.)

6. Louisiana Department of Health and Hospitals. Louisiana Health First. November 14, 2008. http://host.antaresnet.com/cabl/uploads/47.pdf. Accessed October 7, 2013.

7. Louisiana Cancer Research Consortium Website. http://www.louisianacancercenter.org/about-lcrc. Accessed August 24, 2013.

8. Jindal B. A new era for health care in Louisiana. Baton Rouge Daily Report. July 25, 2013. http://www.businessreport.com/apps/pbcs. dll/article?AID=/20130725/BUSINESSREPOR T02/130729879&template=printart. Accessed October 7, 2013.

9. Catalanello R. 6 Louisiana cities among 10 most expensive for health care, report says. The Times-Picayune. August 3, 2013. http://www. nola.com/health/index.ssf/2013/08/six_louisiana_cities_lead_the.html. Accessed October 12, 2013.

10. Behavioral Risk Factor Surveillance System data, Centers for Disease Control and Prevention. http://statecancerprofiles.cancer.gov/risk/index.ph.

Status in the States: In Louisiana, Will Privatization Affect Efforts to Stop Cancer?

Breast cancer patients with PI3KCA mutations are less likely to achieve a pathological complete response (pCR) from dual HER2 blockade in the neoadjuvant setting, according to an analysis of the NEOALTTO trial presented by José Baselga, MD, at the 2013 European Cancer Congress.

The lower pCR rate in PI3KCA-mutant tumors was observed in all treatment arms, irrespective of estrogen receptor (ER) status. “Understanding the mechanism of The pCR rate for the  lapatanib arm was 20.4% for wild-type patients versus14.8% for those with PIK3CA mutations, and for the trastuzumab arm, the pCR rates were 28.4% and 20.0%, respectively.

“Understanding the mechanism of resistance to HER2-targeted agents is a critical step toward identifying the best therapy for individual patients with HER2-positive breast cancer. Activation of the PI3K/AKT survival pathway is one of the molecular mechanisms that contribute to trastuzumab resistance,” Baselga explained.

The study investigated the influence of PI3K pathway mutations (PIK3CA, KRAS, BRAF, AKT1) on sensitivity to trastuzumab (Herceptin), lapatinib (Tykerb), or both agents in combination in early-stage, HER2-positive breast cancer patients enrolled in the phase III NEOALTTO trial. In the main study, dual HER2 blockade achieved a pCR rate of 51.3%, versus 29.5% for trastuzumab alone, and 24.7% for lapatinib alone (P = .0001). The current analysis was based on molecular profiling of 355 NEOALTTO patients.

The primary end point was pCR at surgery, defined as the absence of tumor in the breast. ER-positive and ER-negative patients had similar rates of PIK3CA mutations, at 23% and 22%, respectively.By treatment assignment, PIK3CA mutations were observed in 23% of the lapatinib arm, 19% of the trastuzumab arm, and 25% of the combination arm. Mutations in KRAS were observed in 1 patient (0.3%), and no patient had a BRAF mutation.

PIK3CA mutations were associated with lower pCR rates, most notably in the lapatinib/trastuzumab arm, Baselga reported. For the entire cohort, the rate of pCR was 34% in PI3KCA wild-type tumors, and 21% in PI3KCA mutant tumors (P = .03). In patients treated with the combination, pCR was achieved by 55.8% in those lacking PIK3CA mutations and 28.6% in those patients with mutations (P = .02). The pCR rate for the lapatanib arm was 20.4% for wild-type patients versus 14.8% for those with PIK3CA mutations, and for the trastuzumab arm, the pCR rates were 28.4% and 20.0%, respectively.

A similar pattern was seen in both ER-negative and ER-positive patients. Adjusting for treatment arm and ER status in the logistic regression analysis, significant differences persisted between patients with and without the PIK3CA mutation (odds ratio = 0.45; P = .015). “These data provide further evidence of the role of PIK3CA mutations in resistance to trastuzumab- and lapatinibbased therapies. Thus, assessment of PIK3CA status might be an important tool in identifying patients unlikely to derive substantial benefit from these treatments,” Baselga said.

1. Baselga J, Majewski I, Nuciforo PG, et al. PI3KCA mutations and correlation with pCR in the NeoALTTO trial (BIG 01-06). Presented at: European Cancer Congress 2013; September 27-October 1, 2013; Amsterdam, The Netherlands. Abstract 1859.

Dual HER2 Blockade Less Effective in PI3KCA-Mutant Breast Cancer

Trebananib added to paclitaxel significantly improved progression-free survival (PFS) in patients with recurrent ovarian cancer compared with placebo plus paclitaxel in the large international TRINOVA-1 trial. The addition of trebananib to paclitaxel achieved a 52% prolongation in time-to-disease progression or death, with a median PFS of 7.2 months, versus 5.4 months with placebo

Trebananib (formerly AMG 386) is an investigational anti-angiogenesis recombinant peptide that inhibits the binding of angiopoietin 1 and 2 to the Tie2 receptor—a different target than that of bevacizumab, a VEGF-receptor inhibitor commonly used to treat ovarian cancer. “Anti-VEGF therapy creates a constellation of adverse events. In the TRINOVA series, the idea is to target a non-VEGF angiogenesis factor angiopoeitin 1 and 2.

This strategy has been shown to delay tumor growth and shrink tumors,” explained Bradley Monk, MD, Creighton University School of Medicine and University of Arizona Cancer Center at St. Joseph’s Hospital in Phoenix. Monk reported these results at the 2013 European Cancer Congress in Amsterdam (September 27-October 1, 2013).

“This was a rigorous and closely audited clinical trial conducted at 179 sites in 32 countries. Today, we present the primary PFS analysis and the interim overall survival [OS] analysis. Next year we hope to have the final OS data,” he told listeners.

Patients enrolled in the phase III trial (n = 919) received up to 3 prior therapies and had recurrent disease within less than 12 months of their last prior therapy. They were randomized to a 3 weeks on/1 week off regimen of weekly paclitaxel, with one arm receiving paclitaxel plus placebo and the experimental group being treated with paclitaxel plus once-weekly trebananib 15 mg/kg IV. The average age of patients was about 60 years, and most were Caucasian.  Treatment arms were well-balanced for disease and demographic factors. The majority had grade 2 to 3 cancers; 40% failed on 1 prior therapy; 40% failed on 2; and 20% failed on 3.

In addition to the primary endpoint of PFS in the overall trial, trebananib improved PFS in all subgroups. Response rate was improved from 30% with placebo to 38% with trebananib. Most responses were deemed partial response. At the interim survival analysis, the OS difference favoring trebananib is about 2 months, but only half of the survival events have occurred. Discontinuations were mostly due to disease progression: 87% in the placebo group versus 82% in the trebananib group.

Adverse events of any grade occurred in 96% of placebo patients and 97% of trebananib patients. Edema was the major toxicity of trebananib, experienced by 26% of patients in the control group versus 57% with trebananib (any grade); 5% of the trebananib group had edema of Grade 3 or higher. The incidence of nausea and vomiting was similar in both groups.

In TRINOVA-1, the side effect profile of trebananib did not show increased class effects of VEGF-R inhibition. “The side effect profile of anti-angiopoetin therapy is not similar to that of anti-VEGF therapy [ie, hypertension, proteinuria, wound-healing, complications, and arterial thrombotic events],” said Monk.

Neutropenia and anemia were more common in the placebo arm, and neurotoxicity was more common in the trebananib arm. Monk explained that this was thought to be related to increased cycles of paclitaxel.

1. Monk BJ, Poveda A, Vergote I, et al. A phase III, randomized, double-blind trial of weekly paclitaxel plus the angiopoietin 1 and 2 inhibitor, trebananib, or placebo in women with recurrent ovarian cancer: TRINOVA-1. Presented at: European Cancer Congress 2013 (ECCO-ESMO-ESTRO); September 27-October 1, 2013; Amsterdam, The Netherlands. Abstract LBA41

Trebananib Shows Promise in Recurrent Platinum-Sensitive Ovarian Cancer

Results from a pooled analysis of data from 12 studies have demonstrated a long-term survival benefit that extends through at least 10 years for patients with advanced melanoma treated with ipilimumab (Yervoy).

The results were announced by the drug’s manufacturer Bristol-Myers Squibb on September 27 and presented the next day at the 2013 European Cancer Congress in Amsterdam. This study, which included 2 phase III trials, 8 phase II trials, and 2 retrospective trials, represents the largest overall survival (OS) analysis to date for patients with advanced or unresectable metastatic melanoma treated with ipilimumab.

The analysis included both patients who were previously treated (n = 1257) and previously untreated (n = 604).

 “This pooled analysis is encouraging, particularly when considering that metastatic melanoma is one of the most aggressive forms of cancer and historically, average survival was just 6 to 9 months,” said F. Stephen Hodi, MD, Department of Medicine, Harvard Medical School, Dana-Farber Cancer Institute, in a statement.

In the 1861 patients treated with ipilimumab, median OS was 11.4 months (95% CI: 10.7—12.1). Researchers noted a distinct plateau in OS at year 3 that extended through year 10, independent of line of therapy, ipilimumab dose, or maintenance therapy. The 3-year OS rates were 22%, in the entire study population, 26% for treatmentnaïve patients, and 20% for previously treated patients. The authors of the study wrote that these OS data should be considered as a benchmark for future melanoma therapies, as they represent a large benefit in a difficult-to-treat disease.

“This pooled analysis reinforces the long-term survival data seen in the individual studies and provides additional insight into the overall survival of metastatic melanoma patients treated with Yervoy,” said Brian Daniels, senior vice president, global development and medical affairs, Bristol-Myers Squibb Company, in a statement. “The durability and consistency of long-term survival observed in this analysis is encouraging as we continue to advance the research and development of our immuno-oncology portfolio.”

In each of the trials in the analysis, patients received ipilimumab at different doses, with the majority of patients receiving 3 mg/kg (n = 965) or 10 mg/kg (n = 706) every 3 or 4 weeks. Most of the studies provided the option for eligible patients to receive ipilimumab retreatment or ipilimumab maintenance therapy. Safety data were not included in the analysis. Adverse events attributed to ipilimumab, which are typically mechanism (immune)-based, were managed in individual trials with protocol-specific guidelines, including dose interruption or discontinuation and the administration of systemic corticosteroids.

The FDA approved ipilimumab 3 mg/kg monotherapy in 2011 for patients with unresectable or metastatic melanoma. Ipilimumab is now approved in more than 40 countries. 

1. Schadendorf D, Hodi FS, Robert C, et al. Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in metastatic or locally advanced, unresectable melanoma. Presented at: European Cancer Congress 2013 (ECCO-ESMO-ESTRO); September 27-October 1, 2013; Amsterdam, The Netherlands. Abstract 24.

Pooled Analysis Reinforces Long-Term Survival Benefit With Ipilimumab

A phase III study of the PI3K-delta inhibitor idelalisib in combination with rituximab (Rituxan) has been stopped early following a positive interim analysis, according to a statement from Gilead Sciences, Inc, the company developing the drug announced October 10.

The randomized trial, labeled Study 116, investigated the combination as a treatment for chemotherapy-ineligible patients with previously treated chronic lymphocytic leukemia (CLL). The decision to stop the trial early followed a recommendation from an independent data monitoring committee that found a highly statistically significant prolongation in the primary end point of progression-free survival (PFS). As a result of the stoppage, patients on the control arm receiving rituximab plus placebo are now eligible for treatment with idelalisib in an extension study.

Idelalisib is a first-in-class selective PI3K-delta inhibitor. This mechanism of action is thought to be effective in B-cell malignancies due to the role of PI3K-delta in the activation, proliferation, and survival of B cells. Prior to the phase III investigation, the treatment was explored in early-stage trials, which seemed to confirm this rationale.

“This is the first phase III study to report positive results for a new class of targeted therapies that inhibit B-cell receptor signaling as a major component of their mechanism of action, an important area of focus in the development of chemotherapy-free regimens in CLL and other B-cell malignancies,” said Norbert W. Bischofberger, PhD, the executive vice president of research and development and chief scientific officer at Gilead, in the statement.

The phase III study enrolled a total of 220 patients, approximately 20 patients more than expected. All patients enrolled on the trial had previously treated recurrent CLL with measurable lymphadenopathy. Patients in the trial were randomized in a 1:1 ratio to receive idelalisib at a 150-mg dose twice daily in combination with intravenous rituximab at an initial dose of 375 mg/

 or rituximab and placebo. Patients who progressed were eligible to receive idelalisib therapy in a double-blind extension study.

Data from the interim analysis are likely to be presented later this year. “Given the significant unmet medical need in CLL, particularly in this population of patients who are not fit for chemotherapy, we are pleased that idelalisib has shown a clinically meaningful benefit for patients,” said Bischofberger in a statement.

The phase III study was launched on the basis of results from a phase I trial examining the combination of idelalisib with rituximab and/or bendamustine for patients with previously treated CLL. Results from this analysis were presented at the 2012 meeting of the American Society of Hematology. In that study, 19 patients who had received a median of 2 prior therapies took idelalisib at 150 mg twice daily in combination with weekly rituximab at 375 mg/m

. In the intent-to-treat to population, the overall response rate (ORR) was 78%. Moreover, the 1-year PFS rate was 74%, and 84% of patients experienced a lymph node response (shrinkage ≥50%) resulting in marked reductions in lymphadenopathy.

The highest level of response in this trial was experienced with the combination of idelalisib, rituximab, and bendamustine (Treanda). This portion of the trial contained 15 patients and found an ORR of 87%, a 1-year PFS rate of 87%, and lymph node response in 87% of patients. A randomized phase III study examining the combination of idelalisib, rituximab, and bendamustine is recruiting patients with previously previously treated CLL (NCT01569295).

The early stop of the phase III trial indicates a promising treatment with the potential for regulatory approval. However, controversy exists in medical research regarding stopping randomized clinical trials early based on evidence of benefit. In many cases, evidence suggests that trials that stop early overestimate treatment effects Moreover, an analysis published in BMJ in 2012 found that large overestimates of benefits were common when less than 200 events were analyzed. Most recently, a large phase III trial analyzing abiraterone acetate for men with metastatic castration-resistant prostate cancer before chemotherapy fell under scrutiny after the trial was halted early following an interim analysis.

As a result of this early unblinding, many questioned the authenticity of the survival advantage experienced in the trial, since statistical significance had not been met. Despite this, the US Food and Drug Administration (FDA) approved abiraterone based on results from this study. In its announcement, Gilead stated that it has informed the FDA of its decision to stop the trial. The company is engaged in conversations regarding a potential regulatory filing for idelalisib in CLL.

In September 2013, Gilead submitted a New Drug Application to the FDA for approval of idelalisib for the treatment of patients with indolent non-Hodgkin’s lymphoma (iNHL). That submission was based on data from a single-arm, open-label phase II study of 125 patients with iNHL who were refractory to rituximab and alkylating-agent-containing chemotherapy. In an interim analysis of this study, single-agent idelalisib achieved an ORR of 53.6%, with a median duration of response of 11.9 months. Additionally, median PFS was 11.4 months with lymph node shrinkage experienced in 89% of patients.

In addition to previously treated patients with CLL and iNHL, idelalisib plus rituximab has demonstrated promising results in treatment-naïve patients with CLL, according to results from a phase II trial that was presented at the 2013 ASCO Annual Meeting. In that study, patients who were ≥65 years old with previously untreated CLL or small lymphocytic lymphoma received idelalisib at 150 mg BID combined with weekly rituximab at 375 mg/m2. At a 24-month analysis, the combination was found to be highly active in treatment-naïve elderly patients. The trial found a Kaplan-Meier estimated PFS benefit of 93%. Moreover, the combination achieved a complete response rate of 19% and an ORR of 97%.

At the time of the presentation, the lead author, Susan M. O’Brien, MD, said, “The high overall response rate and durable disease control observed in this phase II study suggest that idelalisib in combination with rituximab could become an important therapeutic option for CLL patients new to treatment.” O’Brien is the Ashbel Smith Professor of Medicine in the Department of Leukemia at the University of Texas MD Anderson Cancer Center in Houston and was a principal investigator of the phase II study.

Positive Idelalisib Data End Late-Stage CLL Trial

The US Supreme Court’s decision to uphold the Affordable Care Act but allow states to decide whether to expand Medicaid

 has raised a question in many states: Where political leaders have been opposed or split on President Obama’s healthcare reforms, is it smart or foolish to cover more people?

While Republicans oppose healthcare reform more often than Democrats, having a Republican in the state house has not always doomed Medicaid expansion. Arizona Governor Jan Brewer, who famously wagged her finger at Obama on an airport tarmac, nonetheless stared down legislators in her own party until they added 300,000 people to the rolls. For New Jersey’s Chris Christie, having a Democratic legislature made Medicaid expansion easier. However, neither Arizona nor New Jersey set up a state-run exchange to enroll people in health plans.

But in other states, philosophical opposition to expanding a government program and concerns about long-term costs forced full-blown rejection of Medicaid Expansion or, in the case of places like Arkansas, Iowa, and Pennsylvania, attempts at hybrid plans. Waivers would allow states to craft their own versions of Medicaid, most with elements of privatization and one, in Pennsylvania, that would require, for the first time, that most new recipients look for work.

On Friday, September 27, Arkansas Governor Mike Beebe received a phone call from US Health and Human Services Secretary Kathleen Sebelius that his state would be the first granted a waiver to pursue a so-called “private option,” which will allow state residents to use Medicaid dollars to subsidize coverage obtained through private insurance. Up to 6 states may pursue some form of Arkansas’ plan with 2, Iowa and Pennsylvania, filing waiver requests.

Beebe, a Democrat, said the waiver would allow about 218,000 Arkansans to receive private coverage. “Our actions have drawn positive attention from across the country, and now we will focus on getting this insuranceto the Arkansans who need it to lead healthier, more productive lives,” he said in a statement.

The Arkansas, Iowa, and Pennsylvania plans all feature free-market aspects to the expansion of coverage—a unique “hybrid” strategy palatable to Republican or conservative Democratic

legislators in their own states, and perhaps to conservative lawmakers elsewhere who have resisted expanding any government program.

September/October 2013

Melanoma: From Impossible to Treat to Poster Child for Targeted Therapies

Challenges in Oncology Practice

Status in the States: In Louisiana, Will Privatization Affect Efforts to Stop Cancer?

Dual HER2 Blockade Less Effective in PI3KCA-Mutant Breast Cancer

Trebananib Shows Promise in Recurrent Platinum-Sensitive Ovarian Cancer

Pooled Analysis Reinforces Long-Term Survival Benefit With Ipilimumab

Positive Idelalisib Data End Late-Stage CLL Trial

New Approaches to Medicaid Expansion: Hybrid Plans Offer Alternatives for Covering More People

Safety Concerns Halt Ponatinib Development

First Generic Version of Capecitabine Gains FDA Approval

Volasertib Given Breakthrough Therapy Designation

Melanoma Combination Granted Priority Review Designation by FDA

In Historic Vote, FDA Backs Perjeta for Pre-surgical Breast Cancer Treatment

Ofatumumab Receives Breakthrough Therapy Designation for Earlier Use in CLL