My recent personal experiences illustrate the current issues for healthcare delivery. Last spring, a driver behind me was blinded by the early morning sun, and she did not see that I had stopped at a stop sign. It only took 4 hours after the rear-end collision for me to develop the aches and pains of a minor whiplash injury. My internist was booked, so I accepted an alternative appointment with a new physician who was 1 year out of residency. My exam was normal except for a neck spasm. My new physician wrote a prescription for some pain medication and a muscle relaxant. Then he began scheduling a magnetic resonance imaging (MRI) scan of the neck.

“Give me a moment,” I asked. “Isn’t my exam normal?”

“Do you really think I have any pathology in my neck based on the history and exam?”

He then explained that he was being cautious; he did not want to miss anything. I told him what I do for a living and explained that I was more than willing to take the meds, rest, and wait to see whether I improved. If I did not get better, I said, I would return for the MRI. We developed a plan for follow-up and shook hands on the agreement.

As I left, he turned the tables on me: “You do realize,” he said, “that your insurers pay me more to do the MRI than to have this discussion.”

Misaligned payment incentives for technology and inadequate payment for discussion and planning encourage physicians to do more rather than less. Even the overrated threat of malpractice is illustrated in this example. In addition, this young physician did not have a forum in which to compare results and costs with his peers, so any quality improvement was left to his ingenuity.

The same issues are exaggerated in medical oncology in which an old payment system has created strong and perverse incentives for care. Medical oncologists evaluate patients with cancer to determine the extent of the disease and then recommend therapy. Treatment options for cancer include surgery, radiation therapy, chemotherapy, or combinations of those 3. If chemotherapy is recommended, the medical oncologist administers those drugs in his office. Medical oncologists purchase chemotherapy drugs at wholesale prices from manufacturers and then bill the payer at retail prices. This payment system originated in the 1960s when few chemotherapy drugs were available and their costs were minimal. However, as more drugs were discovered and as the cost of those drugs increased, a major shift occurred in medical oncology economics. Today, the profit margin from these drug sales accounts for approximately 65% of a medical oncology practice’s income. These profits are essential to cover the overhead of the community oncology office.

The current system does have benefits. The administrative overhead of a dedicated oncology clinic is usually much lower than alternatives in outpatient hospital- based clinics, so they can offer these services for a lower cost. Unpublished UnitedHealthcare (UHC) data show that private offices also use fewer ancillary services for a cancer episode compared with hospital-based outpatient clinics. Combining those 2 factors—cost and use&mdash;has a startling impact. At UHC, the total cost of care for a patient actively on chemotherapy is approximately 2 times higher if the patient is treated in a hospital outpatient clinic than if that patient is treated in a community oncology office.

Unfortunately, there were excesses when profit margins were high. Medicare responded to this problem by lowering chemotherapy reimbursement levels to approximate cost. Using a calculation called Average Sales Price, the federal government pays a 6% margin on its calculatedacquisition cost for each drug. But as with any new payment system, unintended consequences quickly emerged. Even with a fixed margin, the net profit on an expensive drug is higher than that of a low-cost drug. Many generic drugs yielded margins that measured in the pennies whereas new, branded products could generate hundreds of dollars by using the same 6% margin. Not surprisingly, physicians increased the use of expensive chemotherapy drugs. Using Medicare data, Harvard researchers showed that a medical oncologist would prescribe the most expensive regimen when there were multiple choices of therapy.

This incentive has significant implications for total cost. The study noted that each dollar of incremental profit for the medical practice cost Medicare an additional $23 for drug expenditures. With the Medicare decrease in payment, practices started shifting patients to hospital facilities for treatment or shifting their losses to private payers. Private insurers began experiencing inflation trends of 15% annually for cancer care after the Medicare payment change.

A new payment system is needed. When UHC began developing a new pilot payment program to correct the existing problems, it had 3 objectives: (1) separate the oncologist’s income from drug sales, (2) retain the medical oncologists’ personal incomes at current levels, and (3) create an objective performance measurement system that becomes the basis for future payment increases. The pilot started with 5 volunteer medical oncology groups. Each medical group agreed to 2 key requirements to participate. They chose a standard chemotherapy regimen for each of 19 clinical presentations in breast, colon, and lung cancer, and they agreed to participate in a joint performance review with the other participating oncology groups.

Once the groups selected their regimens, UHC calculated the profit margin amount of money each group would make on drug profits for each of the 19 clinical presentations by using the difference between the group’s current fee schedule and the drug costs. A case management fee was added to this amount, and the amount became the patient care episode fee. This new episode fee would be paid on the first day when the patient would receive care from the group. Drugs were reimbursed at cost. The medical group was free to change their drug regimens at any time, but the episode payment would not change. Office visits, chemotherapy administration codes, and other ancillary services—like laboratory tests&mdash;were paid on a fee-for-service basis. Adjuvant treatment episode fees were single payments that covered the time period of the adjuvant regimen. Episode fees for patients with metastatic disease would renew every 4 months, even if the patient elected not to receive additional chemotherapy. UHC is gathering data for clinical and cost profiles of each clinical category. These data are shared openly with all 5 groups. Measurements include complication rates, relapse rates, pain control admissions, and total medical costs. Because each group is treating its patients with a consistent regimen, the pilot creates a comparative effectiveness analysis that allows all of us to identify best practices. If and when a best practice is identified, it is UHC’s expectation that groups will transition care to that practice.

This novel approach accomplishes several important goals. Drug selection is based on best practices rather than income maximization. Oncologists will be able to compare their performance with that of other groups and adopt best practices. UHC anticipates that use of medications with minimal responses will diminish, because physicians will not see any improvement in their clinical performance as they compare data. This program does not penalize the oncologist for participating, because current income is preserved. This method does not address the new drug pricing by pharmaceutical manufacturers. Neither UHC nor the physician community can negotiate effectively when new, single-source drugs are approved for use, because there are no alternatives. In addition, price increases on existing drugs from manufacturers are not addressed.

A second personal experience illustrates why something must be done differently. My son’s roommate—a nursing student at the University of Nevada&mdash;

called me last weekend; she needed help diagnosing a rash for one of her friends. The young nurse was convinced it was the target rash of Lyme disease. Using her cell phone camera, she sent me a photo that could have been used as an illustration in a medical textbook. I gave her my opinion and told her that her friend needed medical care that day. That was when I found out that the patient did not have medical insurance. Although the friend had graduated with a college degree, she was subsisting on 3 different part-time, minimum-wage jobs; none of the jobs offered insurance, and she could not afford the premium if she was going to pay rent, buy food, and put gasoline in her car.

Healthcare coverage is simply unaffordable for too many people. It will only become affordable with radical changes in payment incentives and the elimination of care that does not really matter. The UHC pilot may help, and it may not; it is an experiment. My wish is to see hundreds of experiments in the next 5 years. Only through change are we going to find solutions that work.

 Ingenix of United Health Group, Minneapolis, MN, USA.

The author reports no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.

Concept and design (LNN); and drafting of the manuscript (LNN).

1. Jacobson M, O’Malley AJ, Earle CC, et al. Does reimbursement influence chemotherapy treatment for cancer patients? Health Aff (Millwood). 2006;25:437-443.

Articles

Evidence-Based Oncology

Radical Changes in Payment Incentives and Elimination of Low-Value Care

Trying Something New: Episode Payments for Cancer Therapy 

Analyzing payer management of oncology over the past few years, a major trend has emerged— payers intend to increase their management of the category. Health plans continue to seek methods to curtail the costs associated with cancer care without diminishing the quality of that care. Indeed, both payers and oncologists anticipate significant increases in the aggressiveness of payer oncology management over the next 2 years.

According to the data collected in the most recent edition of 

The Zitter Group’s Managed Care Oncology Index

, just 38% of payers currently feel confident in their organizations’ ability to effectively manage oncology. Although this number represents a significant increase from the 25% who reported such confidence 6 months ago, it is clear that payers have a long way to go to exert extensive control over cancer care.

In anticipation of the expected management increases, oncologists and practice managers indicate a growing resignation to payer influence on oncology practice. However, oncologists also perceive a slight decrease in the level of payer management aggressiveness from 6 months ago. This decline in reported restrictiveness may be due to adaptation by oncologists and practice managers to the policies already in place, as payers do not cite any corroborating changes in policy.

All stakeholders expect the degree of management intensity to ramp up over the next 2 years. Oncologists, however, expect a more dramatic increase than do payers. Sixty-five percent of oncologists expect a high degree of management aggressiveness by 2013, whereas only 21% of payers say they will have highly aggressive management policies in place by then. Oncologists also perceive the current degree of payer oncology management to be significantly more aggressive than payers report. Currently, only 7% of payers report having highly aggressive oncology management policies, whereas 30% of oncologists feel the level of payer management is highly aggressive (Figure 1).

As the cost of oncology care continues to rise, increases in management efforts by payers appear to be inevitable. In fact, payers believe that nearly 23% of current costs could be eliminated from the delivery of cancer care without negatively impacting health outcomes. Oncologists and practice managers share similar sentiments, but not to the degree expressed by payers. Oncologists feel 18% of costs can be shaved, whereas practice managers see that number slightly lower, at just below 16% of costs.

Payers perceive the greatest degree of wasteful spending coming from excessive end-of-life treatment and inappropriatedrug utilization. Eighty-three percent of payers believe inappropriate drug utilization helps to drive excess cost. The majority of payers define inappropriate utilization as utilization outside a compendia-listed use. Conversely, while oncologists believe adherence to compendia improves care, they insist off-label prescribing is critical to providing the best quality care.

Furthermore, 43% of payers see suboptimal distribution of prescription drugs—such as buy and bill versus specialty pharmacy&mdash;as a significant driver of excess costs. That said, only 33% of payers currently require drug distribution through a third-party vendor. The number of plans utilizing specialty pharmacy providers (SPPs) and/or pharmacy benefit managers could see a sizable increase as payers attempt to rein in costs without harming care quality.

During the next year, payers anticipate shifting infused oncology therapy distribution away from buy and bill in favor of their preferred distribution channel, specialty vendors (Figure 2). Currently, more than 70% of infused therapies for oncology are distributed via buy and bill, with average sales price as the primary method of reimbursement used by payers. Providers have felt the pain: 36% of oncologists and 54% of practice managers report declines in practice revenue since moving to average sales price reimbursement. Payers now are looking to SPPs as the next step in minimizing excess reimbursement costs in oncology care.

Already, 30% of practice managers have experienced payer attempts to limit their ability to buy and bill for oncology therapies through contract terms. The majority of these contract terms specified either voluntary or mandatory vendor requirements, eg, specialty pharmacy. This trend has been well established with oral oncology therapy distribution, and payers anticipate a further shift away from off-site retail in favor of the specialty vendor channel for oral distribution over the next year.

Prior authorizations (PAs) remain the most prevalent and impactful management method utilized by payers in oncology management. Although widely used and shown to impact both oncologist and practice manager prescribing behavior, PAs are not fully achieving payer goals. The primary payer objective for oncology PAs is to limit inappropriate utilization, one of the perceived key drivers of excess costs in cancer care. However, just 19% of payers report having met this objective successfully.

There is significant disparity between payer, oncologist, and practice manager perception as to the impact of oncology PAs. While payers believe their PAs take a provider’s office an average of just 16 minutes to complete, oncologists and practice managers report them taking significantly more time, with average durations of 38 minutes and 50 minutes, respectively. Furthermore, payers report denying 38% of all PA appeals, whereas practice managers report that nearly 9 out of 10 appealed requests are eventually approved. Payers and practice managers also differ greatly when it comes to the perceived reasons for a PA denial. Payers report denying PA requests primarily for treatments not on compendia listings/guidelines or the FDA label, whereas over half of practice managers report denials arising due to payer perceptions of a lack of medical necessity. Just 12% of payers report the last to be true (Figure 3).

Although there remains a degree of disconnect between payer management policies and their perceived effect on oncology practices, the reality remains that payers are indeed taking a more direct role in oncology management. In their efforts to decrease costs, payers will continue to increase their use of PA requirements, preferred distribution channels, treatment guidelines, clinical pathways, and companion diagnostics. Oncologists and practice managers seem increasingly, if begrudgingly, to accept these management tools as the inevitable evolution of cancer care management.

The authors (MS, LG, TR) report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.

Concept and design (MS, LG, TR); acquisition of data (LG, TR); analysis and interpretation of data (LG, TR); drafting of the manuscript (MS, LG, TR); critical revision of the manuscript for important intellectual content (MS); statistical analysis (LG, TR); and administrative, technical, or logistic support (MS).

Health Plans Continue to Seek Methods to Curtail Cancer Costs

Payer Management of Oncology Gets Serious

The last thing an oncologist wants to hear is that a medication he or she has prescribed is unavailable. But the reality is that drug shortages, while not new, have reached a crisis level. The medications in short supply run across multiple specialties, but the impact is most prevalent—and devastating&mdash;in oncology.

The American Cancer Society reports that patients with lung, breast, ovarian, and rarer forms of cancer face the biggest health risk when medications like paclitaxel, fluorouracil, doxorubicin, and bleomycin are scarce. An alternate drug may not work as well and there may be increased side effects.

A recent statistic points to the magnitude of the problem: an IMS Institute for Healthcare Informatics analysis found that 550,000 cancer patients were impacted by the drug shortage as of the year ended June 30, 2011.

One of the more prominent leaders working toward a solution is Dr Michael Link, president of The American Society of Clinical Oncology (ASCO). This past summer, Dr Link addressed the drug shortage problem at a Capitol Hill briefing. ASCO’s influence also was evident when, on November 30, 2011, the US House of Representatives Oversight and Government Reform Subcommittee on Health Care, District of Columbia, Census and the National Archives held a hearing on drug shortages. Testimony ranged from declaring the situation a “massive national emergency” to calling on the FDA to accelerate regulatory processes that help resolve drug shortages.

. The ASCO president also serves as the Lydia J. Lee Professor of Pediatric Hematology/Oncology at Stanford University School of Medicine and Director of the Bass Center for Cancer and Blood Diseases at the Lucile Salter Packard Children’s Hospital at Stanford.

Let me start by saying that this is an issue that is not only related to oncologic drugs. It relates mostly to generics, but includes antibiotics and aesthetic drugs as well as oncologic drugs and many others. I think it is now getting more attention because there has been a crescendo effect, almost a tripling of the number of drugs being followed that are in short supply over the last 5 years. There are hundreds of drugs in short supply, versus 20 or 30 in years past.

The reason? That’s a bit more difficult. The companies don’t have to announce the reason for a shortage, so we really don’t know the reason in more than half the cases. Sometimes it’s a manufacturing problem, meaning they’re having difficulty producing a sterile injectible, because that’s what most of the drugs in short supply are. There can be issues the drug precipitates, or a problem with the line. I understand one manufacturing plant was closed down by the FDA because they had a number of problems, and that creates a shortage because there are very few manufacturers making a given drug. If there’s 2 and 1 goes out of business for a while, that creates a shortage.

Q: It sounds like the bigger issue is having some sort of advance notice that you know this is going to happen, so you can make alternative treatment plans.

 Well, now you’re on to the solution, but I want to make sure that another problem is highlighted. That is that there is not much profit to be made on these drugs, certainly the oncologics. If a company is having problems making the drug that would require retooling and expense to solve, and they’re not making much money on the drug, there’s not much incentive to fix the problem. Also, because of the limited profits, these companies may have a different drug they can make, with a better business plan, and so there’s nothing to stop them from just ceasing to make the drug, as a business decision. Given that, the solutions are variable depending on what the real problems are, but economics has to be considered a key factor. Regarding advance notification, companies are not required to notify the FDA they’re going to stop making a drug if it is not listed as a medically necessary drug. Admittedly, if the FDA has advance notice, they can do something preemptively to prevent a shortage. They can explore alternatives like importing a drug from a source outside the United States where the manufacturing is FDA approved, try to induce somebody else to make the drug, et cetera. The longer the lead time, the more clout the FDA might have. The penalties for not notifying the FDA, even if it’s a medically necessary drug, are not terrible, so there’s not much incentive for the companies to let people know. One issue that has been raised is that advance notification actually could exacerbate the problem, because if it’s known a shortage is going to happen, distributors might buy up supplies, and there would be hoarding of drugs both by the hospitals and larger users, as well as distributors.

Q: Can you tell me a little more about the Preserving A ccess to L ife Saving Medications Act? Is that going to help solve this problem so it becomes less of an economic situation for the manufacturers?

 I don’t know if that’s going to solve the problem. One of the key things about this proposal is, number one, to focus attention on the issue. It would certainly do that. Early notification is not going to solve the problem. But, I think this is a good first step. It’s important because at least it’s focusing attention on the issue where we can hope to get to the bottom of the true nature of the drug shortage, and be more intelligent in how we address it.

Q: What kind of impact have you seen when all of a sudden a medication that you need to prescribe to a cancer patient isn’t available? What are the implications there?

 I have faced this situation a couple of times, and it’s devastating. I first became aware of this problem when a drug we used in the treatment of lymphoma became unavailable. I prescribed it, ordered it, and our pharmacy said, “We don’t have any.” That’s when I realized it wasn’t just that drug in short supply, but a number of others, which is how ASCO got into this. In that case, there was already an effective and well-known work-around, an alternative medication that was also available and cheap; it was not on patent, and we could be pretty sure the outcome for the patient would not be affected. The second area where we thought we would run into trouble was in the shortage of cytarabine and daunomycin, which are both necessary to treat leukemia. For these drugs there is no work-around, and not just for pediatricians, but for medical oncologists as well—if you don’t have cytarabine and daunomycin, you just can’t treat the most common form of adult leukemia. And we need them for treatment of childhood leukemia as well. So, this is where there would be a real impact on patient care. The FDA did step in and provide a supply of cytarabine. Our pharmacist got a supply, with the unfortunate consequence that it was obtained at a substantial markup. So, that’s one possible solution. Sometimes the drug is in short supply and there is no workaround, and then one has to consider the unpleasant option of changing a patient’s therapy. That could involve telling a patient we don’t have the drug now, but we could have the drug available, let’s say, next week. That creates additional anxiety.

I think all oncologists know that delaying therapies and increasing the time between therapies is not a good thing. For some patients, even if they have delays they’ll be cured, and for some it may not make a difference, but in the aggregate, we know that having delays in therapy is going to be harmful, that the cure rates of curable cancers will be lowered. An alternative would be to use a substitute. With cisplatin, which is the mainstay drug in the curative therapy for testicular cancer, there’s another platinum analogue available, carboplatin, but it’s less effective. So, we can give a regimen which we know is suboptimal, if you will, but we don’t know the effect it will have on an individual patient. We know that the cure rate for, let’s say, 1000 patients will be less than for cisplatin, but it’s not as if we can’t cure any patient without cisplatin. So, we could do that—with a great deal of anxiety and trepidation.

Q: If you had to use a secondary drug, would you have to use more of it for a greater length of time to have the same impact as your drug of choice?

 I don’t know that we have that information in that kind of detail, but we’d have to use a higher dose. We try to use regimens where we have some track record so we know what to do. In pediatric oncology, for example, we’ve done many studies where we take a standard regimen and add a new drug, and we prove that it adds to the cure rate. It may add 5, 10, 15 percent. We know we can cure some children without that drug if it’s now in short supply; we just know we would be curing fewer of them. But, I don’t know if we know that we could make up the difference by giving the other drugs more intensively, or at a higher dose, or longer. I don’t think we’ve ever done those kinds of studies. We try to prove that a drug adds to the recipe, and then we assume we will have that drug available. One of the horrible things is, we’ve spent a lot of time proving that these drugs work, and now that they’re unavailable, saying to a family, we do know what should be given, but we can’t because the drug is unavailable, is a conversation that is very uncomfortable.

Society will bear the cost, but it’s not clear how it will break down. Let’s start with the example I gave you where our institution was able to get a drug that is necessary, but paid more for it. It’s not clear the patients will get reimbursed for the difference, and it’s not clear that we will bill the difference. The hospital will have to eat that cost because that’s the cost of obtaining the drug which we bear. There are times when a patient will be offered a drug which is a more expensive version. And, of course, that will add cost to the healthcare system. But, that’s what you have to do when a drug is in short supply. Costs that are being added are, first, using a more expensive drug that maybe we think is effective, but which is not on the drug label in terms of its indication for use. The insurance companies may not reimburse the patient for use of the drug. The other costs are, of course, pharmacies and practices spending money, time, and resources rounding up supplies of the drug. And then we know that when you start using drugs that you’re not used to using, you’re going to have to take more time to figure out dosing. It’s not second nature. You have to think about it more, and it also increases the opportunity for errors. If you made a medication error it would certainly add costs and potentially serious problems, and there has been documentation that such things have occurred. Those are additional costs to the system if not to an individual patient.

Q: In talking about other areas that are affected as far as therapeutic areas, are there certain ones prevalent besides oncology, or is it just really across the board?

I think most areas are affected. Anesthetic drugs and antibiotics are among the leading agents, but cardiovascular drugs are affected as well. The reason the cancer drug issue is so compelling is that there are so few work-arounds. We don’t have that many oncologic drugs, and for most of the indications, there are not good, verified substitutes. Whereas one can argue that for most antibiotics there’s an alternative, if you forget about the cost and other details. In anesthesia the argument I would make is, you can still put people to sleep without Propofol, which is one of the drugs in short supply. It’s very convenient, it’s got a good toxicity profile, but there are other drugs we can use, maybe not as conveniently.

In cancer, though, especially in pediatric oncology, without these drugs we really can’t operate. About 80 percent of children with cancer can now be cured almost entirely with these generic drugs that are off patent, and yet many of them are in short supply. It is a crisis because without those drugs we’re back to where we were in the 1960s and 1970s. One disease for example, osteosarcoma, is a tumor where we now cure probably about 70 percent. And yet of the 3 drugs used for the treatment of osteosarcoma, doxorubicin is in short supply, cisplatin is in short supply, methotrexate with leucovorin is in short supply, and the leucovorin rescue which is necessary to give the methotrexate is in short supply. So, if you’re a physician who takes care of osteosarcoma, or a patient, that’s a pretty formidable obstacle.

From our point of view it’s unconscionable when we have a curative therapy that we know about, but we’re unable to deliver it because of the unavailability of a drug which has been around for 20 to 30 years. This is what we’re up against and what is so frustrating for us as oncologists and for our patients.

Q: As ASCO president, do you have more influence?

Yes, I have influence with ASCO. Since we’ve identified this problem, ASCO has been extremely active in advocating for our patients, the people we serve. We were involved in the drug shortage summit in November. In fact, that bill [Preserving Access to Life-Savings Medications Act] really came directly out of the summit. If you look at the legislation and recommendations from this summit, it was almost a cut and paste. So we’re happy to see we had some influence, though we’re not convinced it will solve all the problems related to the shortage. Our government relations staff has been very active on the Hill looking for individual legislators who will take an interest in

this. When we were up on the Hill in May to brief individual congressmen and senators, I was disconcerted to find how few of them really were aware of this shortage. By the time we had this Hill briefing in July it was standing room only. So very clearly this has gained some momentum.

I think it’s important not to create a panic among patients who are already very anxious about their prospects, you know, cancer patients undergoing treatment, because many of them may not be affected by this at all. Their therapies have nothing to do with the drugs that are in short supply, or where they are getting treated the drug supply is not an issue. And for some patients, as in my own example that I gave, there is a very effective and well-known work-around, so their therapy will not particularly be

Q: That’s a huge thing for our audience—cost-effectiveness and still being able to increase quality of care.

Managed care managers should be aware that there are costs to the system which will have an impact on them. Using a substitute may cost more. The procurement charges may be higher because of supply and demand and because hospitals, and practices particularly, are forced to spend more of their resources trying to find sources of drugs. Those all impact the cost of care. Obviously, our major concern is the effect this is having on cancer care in our country. It’s not just confined to the United States, it’s a problem elsewhere also, so we’re hoping we can come to some sort of creative solution. It will be a combination of entrepreneurial things, legislative things, it’s going to be more than 1 solution to this problem, but we hope it can be solved before it becomes a larger crisis.

Dr Link reports receiving grants from Seattle Genetics and pending grants from Pfizer, none of which pose a conflict of interest with the subject matter of this article.

Grim Reality Is a Bitter Pill to Swallow: Interview with Michael P. Link, MD, ASCO President

Unraveling the Complexity of Drug Shortages

This year, we mark the 40-year anniversary of the National Cancer Act. The law expanded the scope and funding of the National Cancer Institute, among other initiatives, in what has become known as the “war on cancer.” Looking back over the years, it is indisputable that we have made dramatic inroads in fighting cancer. A just-released report by the Centers for Disease Control and Prevention estimates that the number of survivors of cancer in the United States has increased from 3 million in 1971 to 11.7 million in 2007.1 Yet cancer still claims the lives of more than half a million Americans each year and ranks close behind cardiovascular disease as the leading cause of death.2 In this article, we offer our perspectives on how the war on cancer is going from the clinical and policy front lines and speculate on what the future holds.

Battles Have Been Won, With Some Impressive Results

There is little debate that cancer care delivery in the United States has evolved dramatically in the past 40 years and has produced impressive results. Aided by therapeutic and delivery advances, fellowship-trained oncologists have set up private practices across the country that have moved cancer care from the inpatient, academic center complex to the outpatient, community setting. Today, 4 of 5 Americans battling cancer are treated close to home in independent practices or those affiliated with hospitals.3 The community model of cancer care has provided high-quality, affordable, and accessible treatment to patients with cancer.

Oncologists have been aided by significant advances in how they diagnose, treat, and manage cancer. For instance, the death rate from breast cancer decreased by approximately 2% per year between 1990 and 2006.4 The multifactorial reasons for this decrease include widespread use of screening tests—such as mammography, which has increased early detection&mdash;as well as improvement in treatment in the adjuvant and metastatic setting. We can now realistically talk about certain metastatic cancers as chronic diseases, given that patients often live many years with good quality of life.

These encouraging results extend to the entire population. The increase in cancer mortality rates has been reversed, and 5-year survival rates for the United States demonstrate the strength of our cancer care delivery model. For example, American women have a 63% chance of living for at least 5 years after a cancer diagnosiscompared with 56% for European Because of reimbursement cuts from both federal and private payers and the general economic climate, oncology practices are being forced to operate in an environment of tremendous uncertainty. Any type of business planning beyond the current year is meaningless and makes running the business side of an oncology practice difficult at best. A practice impact tracking report shows that 199 cancer treatment sites have closed during the past 3 years, and an additional 369 oncology practices are under financial pressure.7 With the unpredictability of revenue streams and adverse market conditions, momentum is building for alternative affiliations. Many oncology practices are entering into arrangements with hospitals that include outright purchase, professional service agreements, and comanagement opportunities. It is possible that such arrangements may influence patient access to care in the future. The greatest uncertainty facing oncologists and all physicians is the extent to which the ACA will be implemented. Republicans in Congress have launched a legislative assault to defund and repeal provisions in the law, and the Supreme Court is likely to decide whether the cornerstone of reform—the mandate that will require all Americans to have insurance or pay a penalty&mdash;is constitutional. Regardless of the final fate of the ACA, it is clear that this landmark legislation has already profoundly influenced the thinking of practices, hospitals, and payers, given the emphasis on coordinating care and promoting quality and cost-effective initiatives in medicine. Oncologists’ Drive to Innovate Gives Hope

Just as oncologists created and evolved the world’s best cancer care delivery system, this culture shift has inspired many to further innovation despite the chalwomen; American men have a 5-year survival rate of 66% compared with a rate of only 47% for European men.5

Public Policy May Stand in the Way of Victory 

Unfortunately, public policy has changed the reimbursement model for Medicare, which accounts for approximately half of the payments for cancer care and threatens the advancements made to date. The intent of the Medicare Modernization Act of 2003 was to better balance the payment for cancer drugs and medical services. However, the law left shortfalls in the reimbursement of services, which have been exacerbated by additional payment cuts made by the Centers for Medicare & Medicaid Services. A study that was based on actual practice costs and completed by the policy firm Avalere Health estimated that Medicare reimbursed only 57% of the cost of delivering cancer care in 2009.6

Because Medicare is such a large payer, it exerts inordinate influence over the reimbursement system, with an escalating number of private payers following Medicare

rates. It is increasingly difficult for private practices to operate under conditions in which Medicare reimbursement prevails. As a result, noncompensated but critical services—such as nutrition and counseling&mdash;are being abandoned as a result of lack of funding. Compounding the shortfalls in the reimbursement of cancer care is Congress’ inability to fix the overall Medicare payment system on the basis of the sustainable growth rate (SGR). After a series of short-term patches during 2010, Congress managed to pass a bill averting a severe cut in Medicare payments until January 1, 2012. If Congress does not act to patch or fix the flawed SGR-based payment system, a 29.5% cut in Medicare rates will become effective.

Further clouding the environment for oncology is the Patient Protection and Affordable Care Act (ACA), the healthcare reform bill that passed into law in 2010. The law includes some positives for cancer care, such as the elimination of annual and lifetime insurance caps, coverage for preventive services like colonoscopy and mammography, and prohibition of exclusion of the routine costs of cancer care for patients in clinical trials by private insurers. However, several provisions in the law are disconcerting to oncology practices. Chief among these is the creation of the Independent Payment Advisory Board, which is charged with simply cutting Medicare spending to providers when certain targets are exceeded—a type of SGR on steroids.

Because of reimbursement cuts from both federal and private payers and the general economic climate, oncology practices are being forced to operate in an environment of tremendous uncertainty. Any type of business planning beyond the current year is meaningless and makes running the business side of an oncology practice difficult at best. A practice impact tracking report shows that 199 cancer treatment sites have closed during the past 3 years, and an additional 369 oncology practices are under financial pressure.7 With the unpredictability of revenue streams and adverse market conditions, momentum is building for alternative affiliations. Many oncology practices are entering into arrangements with hospitals that include outright purchase, professional service agreements, and comanagement opportunities. It is possible that such arrangements may influence patient access to care in the future.

The greatest uncertainty facing oncologists and all physicians is the extent to which the ACA will be implemented. Republicans in Congress have launched a legislative assault to defund and repeal provisions in the law, and the Supreme Court is likely to decide whether the cornerstone of reform—the mandate that will require all Americans to have insurance or pay a penalty&mdash;is constitutional. Regardless of the final fate of the ACA, it is clear that this landmark legislation has already profoundly influenced the thinking of practices, hospitals, and payers, given the emphasis on coordinating care and promoting quality and cost-effective initiatives in medicine.

Oncologists’ Drive to Innovate Gives Hope

Just as oncologists created and evolved the world’s best cancer care delivery system, this culture shift has inspired many to further innovation despite the challenges placed in their way. Consultants in Medical Oncology and Hematology in Drexel Hill, Pennsylvania, which is led by John Sprandio, has reengineered its approach to become the first community oncology practice in the country to earn the highest, level III recognition from the National Committee for Quality Assurance

under its Patient-Centered Medical Home Program.8 At the time of diagnosis, physicians in this practice assume primary responsibility for the patient’s cancer treatment as well as for the coordination of all the patients’ other medical care, extending through the development and implementation of a survivorship plan. At the heart of this patient-centered medical home model are specific definitions of quality and value in the delivery of cancer care. The promise of healthcare reform—namely, enhancing quality and controlling costs&mdash;is becoming a reality.

Other community oncology practices are pursuing novel innovative reimbursement initiatives with payers in attempts to forge win-win relationships that preserve and foster the delivery of quality cancer care. Several practices from around the country are working with UnitedHealthcare on a program built around agreedupon treatment guidelines and episodes of care for 19 different cancers and disease states on the basis of stage of cancer. In this scenario, the drugs become a passthrough item and are not the drivers of operating margin. Risk is shared by both the practice and the managed-care organization. By comparing actual with planned use within and across practices, this program has the potential to continually provide guidance to move toward best treatments for specific diseases and stages.

Other practices are looking to increase participation in networks that clinically integrate care by using prespecified care plans that are based on national practice guidelines. In oncology, there is a strong evidence base that focuses on clinical trial—tested regimens, which are constantly updated by such authorities as the National Comprehensive Cancer Network and the American Society of Clinical Oncology. These guidelines offer the opportunity for oncologists, who are among the most prevalent adopters of electronic health records in medicine, to continually monitor compliance with process in treating patients according to prespecified plans and to scrutinize patient outcome. Community oncologists are thus well poised to be leaders in accountable care organizations, as these are formed under hospital, payer, or physician leadership.

This fundamental change in the way cancer care is organized and delivered comes against a background of groundbreaking discovery into the basic biology of cancer. The understanding that a finite number of critical oncogenes and pathways drive cancer growth and metastasis has reached a level at which rational therapeutics can be designed against cancer tissue—specific targets, enhancing efficacy and reducing toxicity. Already, early fruits of this labor have been recognized with US Food and Drug Administration approval of multiple agents against previously difficult- to-treat cancers such as renal cell carcinoma. Recognition that every tumor type is itself composed of multiple subsets that are driven by different mutations with each possibly requiring a different approach will actually add to the complexity of ensuring appropriate care, as the decision tree and system support needs will be large. Improvements in health informatics that are user friendly and easy to implement in the clinic hold the promise to aid in care delivery and allow monitoring of quality cancer treatment in the emerging age of personalized cancer care.

Public Policy May Decide the Outcome of the War

There is no doubt that we have made positive inroads in terms of winning the war on cancer. The tools are in place and increasing in both sophistication and

precision for additional progress toward making cancer a true chronic disease if not ultimately to find cures. We question, however, whether public policy will erect insurmountable barriers that ultimately make winning the war difficult if not impossible. With an increasing demand for cancer care that is driven by the demographics of an aging population that is far outpacing the supply of oncologists and the ongoing transformation of the reimbursement system, the challenges facing oncology are formidable. The first stage of the war involved scientific advancements, ingenuity, and entrepreneurial spirit in developing the cancer care delivery system that is the model for the world. The next stage will require the collaboration of oncology providers and payers to explore innovative ways of preserving and developing the model even further to foster quality and cost-effective cancer care.

 Ted Okon, MBA, is Executive Director, Community Oncology Alliance. Lee Schwartzberg, MD, FACP, is Medical Director, West Clinic.

The authors (TO, LS) report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.

Concept and design (TO, LS); and drafting of the manuscript (TO, LS).

1. Centers for Disease Control and Prevention (CDC): Cancer Survivors - United States, 2007. MMWR. 2011;60:269-272.

2. American Cancer Society: Cancer Facts & Figures, 2010. http://www.cancer.org/acs/ groups/content/@nho/documents/document/ acspc-024113.pdf.

3. National Cancer Institute; NCI Community Cancer Centers Program (NCCCP). Pilot Program Summary—January 2007.

4. Jemal A, Siegel R, Xu J, et al. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277-300.

5. Verdecchia A, Francisci S, Brenner H, et al. Recent cancer survival in Europe: a 2000-2002 period analysis of EUROCARE-4 data. Lancet Oncol. 2007;8:784-796.

6. Jauch S, Dietz K, Bazile M, Hughes K; for the Community Oncology Alliance. Providing High Quality Care in Community Oncology: an Assessment of Infusion Services and Their Associated Costs. Avalere Health Web site. http://www.avalerehealth.net/research/ereport.php?rid=1044. Published February 2009.

7. Community Oncology Alliance: community oncology cancer care practice impact report: documented impact on community oncology practices. http://www. communityoncology.org/UserFiles/files/e6c14902-aebb-4368-8d8f-b14234f95161/COA%20Community%20Oncology%20Practice%20Impact%20Report%207-23-10.pdf.

8. Sprandio JD. Oncology patient-centered medical home and accountable cancer care. Community Oncol. 2010;7:565-572.

The Challenges Facing Oncologists Are Formidable

Are We Winning the War on Cancer?

The University of Michigan (U-M) Center for Value-Based Insurance Design (V-BID) has been gaining momentum since its 2005 launch, guiding efforts to support the development, implementation, and evaluation of innovative health benefit designs balancing cost and quality. Since that time, numerous private and public employers, unions, and business coalitions nationwide have implemented value-based insurance design approaches. V-BID has been recognized as an important public policy measure for balancing costs and quality in healthcare at the local, state, and federal level. V-BID was incorporated into federal health reform law—Section 2713 (c) of the Patient Protection and Affordable Care Act, which passed in 2010.

The foundation of value-based insurance design is rooted in removing barriers to essential, high-value health services. V-BID programs improve health outcomes at any level of healthcare expenditure. Studies show that when barriers are reduced, significant increases in patient compliance with recommended treatments and potential cost savings result.

In the following interview, A. Mark Fendrick, MD, one of 3 co-founders of the U-M Center for Value-Based Insurance Design (www.vbidcenter.org), discusses V-BID and its value in oncology, along with Jonas de Souza, MD, instructor of medicine, Section of Hematology/Oncology at the University of Chicago Medical Center.

 The basic V-BID premise is to align patients’ out-of-pocket costs, such as co-payments and premiums, with the value of health services. This approach to designing benefit plans recognizes that different health services have different levels of value. By reducing barriers to high-value treatments (through lower costs to patients) and discouraging low-value treatments (through higher costs to patients), these plans can achieve improved health outcomes at any level of health care expenditure.

In oncology, V-BID would further consist of a reimbursement model that promotes evidence-based medicine. At the same level of health care expenditure, it would promote a higher utilization of interventions with higher efficacy and/or with a higher level of evidence, as shown in clinical trials, at a cost of a lower utilization of interventions with marginal benefits and those that are not supported by evidence.

In general terms, value is the right therapy to the right patient at the right time, at the right cost. In other words, value has several domains, which include: a) the safety of the intervention, where toxicities should be kept to a minimum; b) efficacy and effectiveness, where interventions with incremental proven benefits, as shown in clinical trials, should be considered of value; c) out-of-pocket cost to the patient and costs to society, where an intervention that is safe and has efficacy should not place a cancer patient under a financial strain. There have been several discussions among stakeholders about the definition of value, but as ground rules, the wrong value is when the intervention provides no incremental survival or quality of life benefit; when the intervention has an unacceptable toxicity profile; or when a life-saving or prolonging intervention is out of reach to a particular patient for financial reasons.

In addition, there is lots of evidence that suggests that patients do not always use high-value, potentially lifesaving oncology services, even when they face no financial barrier. However, it is also well established that when patient barriers are reduced—such as in a V-BID plan&mdash;utilization of these services will increase significantly.

What would be examples of how V -BID can be applied in practice?

 If any intervention were to be demonstrated to enhance clinical outcome (our primary goal) or constrain healthcare expenditures, it would be included in a value-based approach. V-BID programs outside of cancer have rapidly expanded beyond drugs, to include screenings, diagnostic tests, and specific clinician groups and delivery systems. Certain V-BID programs encourage patients to receive care at cancer centers of excellence, because of their superior quality, not because they cost less.

 In practice, a system where a screening colonoscopy in a 30-year-old man with a genetic syndrome predisposing to colorectal cancer, such as hereditary nonpolyposis colorectal cancer, should be done at virtually no cost to the patient. On the other hand, the same procedure, performed electively in another 30-year-old man with no predisposing risk factors, should have a higher copayment. Or, in the therapeutic realm, if intervention X provides a median survival benefit of 4 months in metastatic colorectal cancer, it should be valued more and have its copayment lowered and access improved to patients, when compared with the same intervention providing 2 months of incremental survival in metastatic non— small cell lung cancer.

Under the V -BID model, what are some recommended high-value alternatives for managing end-stage cancer?

The sooner we move to a more “clinically nuanced,” efficient and effective cancer delivery system, the better off all stakeholders will be. That is why we feel that patient out-of-pocket costs should not be exclusively based on the cost of a service, but instead be tied to the amount of clinical benefit for the money spent.

An easily overlooked and undervalued intervention in managing patients with advanced malignancies, when usually all therapeutic interventions have failed, is early introduction to palliative care services. They have been shown to improve survival and quality of life in this group of patients but still are undervalued when compared with more commonly prescribed, and usually off-evidence, therapeutic approaches. Patients should have access to these interventions facilitated.

Is there any movement from the stakeholders toward better aligning the value of oncologic interventions with patients’ out-of-pocket costs?

The most important step forward is the regulations in the Affordable Care Act [Section 2713] supporting evidencebased cancer screenings being provided to all Americans without any cost sharing. Preventing cancer is their first focus; it is our hope that future endeavors will address treatment as well.

V-BID does not focus only on specific interventions. The recent trend in oncology toward clinical pathways is a similar model. In this system, payers promote interventions, usually therapies, which are shown to have improved outcomes at reduced costs, by giving financial incentives to providers and/or groups of practices to prescribe them. V-BID would also encourage the greater utilization of these services by facilitating access and/or providing incentives to patients to use these high-value interventions.

 From University of Michigan Medical Center (MF), University of Chicago (JDS).

The authors (AMF, JDS) report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.

Insights Into Value-Based Insurance Design in Oncology

Putting Value Into Practice

Melanoma is one of the most frequent cancers; more than 2 million Americans are treated for skin cancer annually. However, in its earlier stages, it can be easily cured by removal of the skin lesion.

 “Melanoma is on the surface of the skin and therefore easily visible to patients, doctors, and other health professionals without the use of x-rays or invasive procedures,” said Lynn Schuchter, MD, professor of medicine, University of Pennsylvania School of Medicine, Philadelphia. “Therefore, early detection is highly feasible. Most melanomas are cured with surgery because the melanoma is detected at an early stage of disease, before melanoma cells have the potential to metastasize.” Schuchter explained, “Once melanoma metastasizes to distant sites, it is highly resistant to therapy.” It caused an estimated 8700 deaths in 2010.

Chemotherapy for advanced disease has yielded poor 5-year survivals for patients with metastatic disease—16% of those with metastatic melanoma survive 5 years post-diagnosis.

 Dacarbazine is the only drug approved by the US Food and Drug Administration (FDA) for treating metastatic melanoma, and it is often ineffective.

 In other words, the prognosis for patients whose melanoma has spread is generally poor, and very few therapies existed before 2011 that could make more than a marginal difference. Only recently have investigational products emerged that, alone or in combination, seem to yield positive responses in some patients.

Taking Advantage of the Body’s Immune Response

Melanoma is one of the few cancers that trigger the body’s immune response naturally. 

 The problem is that the response is easily overwhelmed by the malignancy. Ipilimumab, which was approved in March 2011 by the FDA, works by spurring the body’s immune system to attack the tumor. The melanoma pipeline comprises several examples of investigational agents that seek to enhance the immune response, including therapeutic vaccines.

 The therapeutic vaccine that is perhaps furthest along the pipeline is OncoVEX

, which is customized to the patient by using their own tumor antigens. This viral vaccine invades both healthy cells and melanoma cells, but it does not harm the healthy cells, only replicating within the malignant cells, according to the manufacturer, Biovex, which was acquired by Amgen in March 2011.5 The virus produces granulocyte- macrophage colony-stimulating factor (GM-CSF), which gathers dendritic cells, causing the rupture of the tumor cell. This releases GM-CSF and tumor-cell peptides into the local area. The dendritic cells collect the tumor-cell peptides, allowing the immune system to recognize and attack them.

In 2009, phase II testing of the vaccine in 50 patients with metastatic melanoma revealed overall survival at 2 years of 52%, and an objective response rate was 26% (stable disease rate of 20%).

 Phase III testing is currently under way, and this OPTiM trial is expected to be completed in June 2012 (ClinicalTrials.gov, NCT00769704). The OPTiM trial compares the vaccine with the use of GM-CSF administered subcutaneously in patients with stage III (b-c) and stage IV (M1a-c) disease.

 Not all autologous vaccine-based therapies entering phase III trials have met with success. This vaccine (formerly known as Oncophage), which is developed using gp

 and other peptides from the patient’s own tumor, was found to not improve survival in patients with stage IV melanoma compared with any other choice of therapy by the physician. In this phase III trial, only patients with better prognostic characteristics who were injected with vitaspen seemed to improve.

In the case of MVax, from Avax Technologies, the phase II clinical trial results were encouraging, yet the phase III study was halted in 2010, not for safety reasons or poor outcomes, but because of a lack of capital. It is unclear as to when or if this phase III trial may be continued, or if an interim analysis of the study results will take place as planned.

Similarly, in 2005, CancerVax Corphalted its phase III trial of the vaccine Canavaxini for late-stage melanoma not because of safety reasons but because it had not shown any benefit over placebo.8

Schuchter commented that overall, “Current approaches to vaccine development are still a major challenge. Unless there is a whole new approach to melanoma vaccines, I am not optimistic about the future of vaccines for patients with melanoma.”

 A plasmid that contains the genetic sequences for HLA-B7 and β2- microglobulin, Allovectin-7 is a receptor that activates T cells to provoke an immune response.

 This immunomodulator can be injected directly into the tumor lesion, which may help T-cell recognition of the malignancy and specific attacks on these specific tumor cells.

In phase II studies, Allovectin-7 injection in patients with recurrent or refractory advanced melanoma produced a 12% response rate, with a median duration of response of 13.8 months.

The phase III AIMM trial was begun in 2007 and compares Allovectin- 7 with dacarbazine or temozolomide in patients who had not been previously treated with chemotherapy (ClinicalTrials .gov, NCT00395070). This trial is scheduled for completion in the third quarter of 2012.

 GSK2132231A is a recombinant fusion protein with potential immunostimulatory and antineoplastic properties that is derived from the melanoma antigen MAGE-3 and protein D from 

e (it is also referred to as a MAGE-3 + AS02B by the manufacturer). No clinical trial data using this agent have yet been made public, but a phase III trial called DERMA is currently enrolling patients to examine the use of GSK2132231A as adjuvant therapy for patients with resected melanoma (ClinicalTrials.gov, NCT00796445). Thirteen hundred patients will be enrolled, and the study is expected to be completed in December 2016.

 This product, a fully human IgG2 monoclonal antibody targeted to CTLA-4, like ipilimumab, may summarize the key learning of research on melanoma to date: The shotgun approach to drug development in metastatic melanoma works poorly. In a previous phase III trial, tremelimumab failed to demonstrate a significant improvement in overall survival compared with temozolomide or dacarbazine in a cohort of patients without prior systemic treatment for their metastatic melanoma.

However, Pfizer came to an agreement with Switzerland’s Debiopharm to revive plans for a clinical trial of tremelimumab in patients with a biomarker indicating it would most likely be effective. Under this arrangement, Debiopharm would be responsible for funding and running the phase III trial (not yet under way).

 In October 2011, Pfizer granted global rights to the product to MedImmune, a subsidiary of AstraZeneca, for development of this product for other indications.

Approved in March 2011 for use in non-resectable or metastatic (untreated) melanoma, its manufacturer, Bristol-Myers Squibb, is conducting additional trials to determine if ipilimumab is also effective in untreated metastatic disease when combined with dacarbazine (ClinicalTrials.gov, NCT00324155) and if it is effective as adjuvant therapy in patients with high-risk stage III disease (ClinicalTrials.gov, NCT00636168). Randomized phase II data have demonstrated 65% 1-year survival and 23% 3-year survival for the ipilimumab + dacarbazine combination in patients with chemotherapy-naïve advanced disease.

Ipilimumab is a fully human monoclonal antibody targeted to CTLA-4, a molecule known to negatively regulate the immune system.

 By inhibiting CTLA-4, ipilimumab can enhance the immune system’s T-cell response to tumor cells. In its pivotal 3-arm trial, another BMS agent, gp100 peptide vaccine, which was dubbed MDX-1379, was used as the active control, despite the fact that no standard of care exists for this patient population. Patients were randomized to receive ipilimumab and gp100, gp100 and placebo, or ipilimumab and placebo. Compared with the median overall survival (OS) of the gp100 arm (6.4 months), both ipilimumab- containing arms produced significant improvements, with a median OS of 10.0 months in the combination therapy arm (

 <.001) and 10.1 months in the monotherapy arm (

 =.003). In addition to these promising data, ipilimumab is also in phase III testing as an addition to dacarbazine chemotherapy for patients with untreated advanced melanoma (ClinicalTrials. gov, NCT00324155). Clinical trials have identified potential toxic liver effects.

There is no evidence that BMS is proceeding with the developmental program for MDX-1379.

Much research in metastatic melanoma has involved testing of agents on specific melanoma cell targets or biomarkers. The targeted medication that has received the most attention, vemurafenib, was approved along with its companion diagnostic test in August 2011 to treat patients with metastatic (late-stage) or unresected (inoperable) melanoma in patients whose tumors express the BRAF gene’s V600E mutation, a driver of tumor growth. Other targets include c-kit, MEK, and Bcl-2 inhibitors. However, successful targeting is difficult, as demonstrated by Genta, which in May 2011 terminated its Phase III trial and development program for the Bcl-2 inhibitor oblimersen (Gentasense) for the treatment of melanoma.

 On the other hand, GlaxoSmithKline’s GSK2118436, a BRAF inhibitor, has entered Phase III testing (the first Phase III study is scheduled to be completed in June 2012), which if successful in clinical trials won’t reach the market for some time (2014 at the earliest).

 Another targeted agent, GSK1120212, is an inhibitor of the MEK1 and MEK2 (MEK1/2) enzymes, preventing Raf-dependent MEK phosphorylation, resulting in antitumor effects in early-stage trials.

 This GlaxoSmithKline product is the subject of multiple clinical trials for different oncology indications. For melanoma, it is being tested in an open-label, randomized Phase III study comparing GSK1120212 with chemotherapy (eitherdacarbazine or paclitaxel) in up to 297 patients with stage IIIc or stage IV malignant cutaneous melanoma (all having a BRAF mutation—positive tumor). This trial is not scheduled for completion until September 2012 (ClinicalTrials.gov Trial Number NCT01245062).

Developed by Plexxicon and Roche, this BRAF V600E inhibitor seems to be effective

—in some cases, dramatically effective&mdash;for patients with this mutation, though its effects seem to wane after a period of time.

In previous studies, vemurafenib had induced response rates of 50% and more in patients with metastatic melanoma who have the BRAF V600E mutation. In the phase III BRIM3 study, this oral agent (960 mg bid) was compared with intravenous dacarbazine (1000 mg/m2 of body surface area) every 3 weeks as monotherapy in 675 previously untreated patients with stage IIIC or IV melanoma.

After 6 months of treatment, vemurafenib demonstrated an OS of 84% compared with 64% in the dacarbazine group. In the interim analysis for OS and final analysis for progession-free survival (PFS), vemurafenib demonstrated a 63% relative reduction in risk of death from melanoma compared with dacarbazine. Response rates were 48% for vemurafenib and 5% for dacarbazine (

 <.001). In addition, the risk of the composite end point, death or disease progression, was 74% lower in the vemurafenib group (

However, this agent is not without significant side effects. Thirty-eight percent of the study population taking vemurafenib required dose adjustments to alleviate side effects such as photosensitivity skin reactions, arthralgia, and fatigue.

Although this study did not report long-term follow-up, there is anecdotal evidence that patients who benefit from vemurafenib may not experience a recurrence for 7 months to 2 years or more.

With the recent progress in treating metastatic melanoma using targeted therapies like ipilimumab and vemurafenib, might combination approaches of these 2 be next in line for clinical trials? Samjiv S. Agarwala, MD, at St. Luke’s Cancer Center said, “Combination therapy would be an interesting research approach given the differences between ipilimumab (low response rate, prolonged duration) and vemurafenib (high response rate, possibly less durable).” Agarwala pointed out, however, that “Future trials with other agents in combination should address specific biomarkers.”

A study to test this combination of vemurafenib and ipilimumab is listed on Clinical- Trials.gov but is not currently under way. Additionally, it is expected that the use of vemurafenib will be tested in coming years in a phase IIII study as adjunctive therapy in patients with metastatic melanoma.

There are few positive data to report on conventional chemotherapeutic agents in the treatment of metastatic melanoma. One of the few, tasisulam, has run into safety problems in phase III testing.

Tasisulam is an acyl-sulfonamide compound which induces apoptosis through the mitochondrial-mediated cell death pathway. In phase II trials, 47% of patients taking tasisulam experienced some level of disease control, and a 2.6-month PFS (median) as second-line treatment of patients with unresectable or metastatic melanoma.

 This was not a controlled trial. In December 2010, the SUMMIT-1 phase III registration trial of tasisulam versus paclitaxel stopped recruiting patients with metastatic melanoma because of 12 patient deaths that were potentially associated with the medication. 21 There is no further word from the manufacturer (Eli Lilly) whether dosing will be changed for continued enrollment or whether the trial has been discontinued permanently.

Although the late-stage pipeline for melanoma seems bustling, most of the interest is occurring around ipilimumab and vemurafenib, which have been approved for their initial indications.

A New Era in Targeted Treatment Has Begun

Targeted Products Yield Most Promising Results

It’s hardly shocking that physicians have generally resisted moving over to electronic health records (EHRs). Cost concerns and well-founded wariness over the lack of standards-based interoperability among many EHR systems has prevented many a doctor from making the leap.

The problem is that healthcare information technology isn’t going away. In fact, much like an aggressive disease, it’s only going to grow stronger. Health reform and its ever-evolving changes are quickly transforming the EHR conversation from one of “I’ll stick with paper” to “I’d best do this if I want my practice to be fully efficient.”

The value gained from carefully researching and employing an EHR system is worth the investment, especially for oncologists, who are managing a gravely sick patient population.

The US Oncology Network is one of many oncology-based organizations that advocate for the use of healthcare information technology, encouraging physicians to embrace the array of benefits that lead to fewer errors, better targeted care and improved outcomes, access to vital life-saving treatments, and the latest research.

The Oncology Electronic Health Record Field Guide

 a publication of the American Society of Clinical Oncology (ASCO), encourages oncologists to adopt an oncologyspecific EHR rather than a generic one. For economic reasons, however, some oncology practices have opted for generic EHRs that have been tailored to their needs. But going this route carries the risk of not having the full menu of critical features that oncologists need. Plus, it’s still likely that even oncology-specific EHRs will need to be customized within the subspecialties. For example, surgeons may not have much use for an EHR with a prescription-writing function because they typically prescribe only a handful of formulary medications for a limited amount of time, as opposed to medical oncologists whose chronically ill patients need multiple drugs. Each oncologist should pick and choose the functionalities they need, as laid out by ASCO:

• Tumor staging—Tumor-Node-Metastases (TNM) nomenclature and others

• Multidisciplinary and data-intensive work flow—pathology, lab, imaging

• Chemotherapy dosing and administration

• Clinical trial and protocol management

Yet another benefit to employing an EHR is the fact that payers are giving closer attention to pay for performance (P4P). Knowing this, oncologists should be further encouraged to adopt the technology to ensure the efficient incorporation of consensus measures of quality and the use of best practice tools.

Some EHRs include a patient portal application, enabling the physician to gather a patient’s medical history before the first visit. With the portal, an individual’s medical data can be directly uploaded into the EHR and become part of the permanent record.

Additionally, with some systems, patients can establish and manage a separate personal health record (PHR), either as part of the EHR or as a separate Webbased tool. PHRs can store treatment history, making it simple for other medical facilities to capture and use the information.

From a physician-to-physician standpoint, The US Oncology Network offers a Web-based community called “The Oncology Portal,” which allows its member physicians to collaborate in real time.

The following summary is from Navigating Cancer, Inc, an oncology-specific, HITECH- certified patient portal

Hematology Oncology Consultants, PA, is an established practice with 6 oncologists and 2 locations in the Orlando, Florida, region. They had not yet adopted an EHR and were looking for a solution that could help them achieve 3 goals:

• Offer their patients electronic access to their medical records and solve additional criteria to help them qualify for the federal HITECH Act Meaningful Use incentives.

• Begin capturing patient information in a structured database that had the flexibility to integrate with any future EHR vendor they selected.

• Find a cost-effective solution that would improve their new patient registration process while providing them with hard cost savings.

After implementing the patient engagement portal, the practice realized the following results:

• New patients register online from home, where they have access to their medical history, resulting in more complete and legible forms.

• Patient information now captured in a structured database, and once integrated with an EHR, will provide patients with access to their medical records online, both requirements to qualify for the Meaningful Use incentives.

• Patient education materials now delivered electronically, another requirement to qualify for the Meaningful Use incentives. Eliminated the need for paper materials, freeing up storage space in the clinic.

Why Oncologists Must Tailor Clinical Features to Their Needs

February

Trying Something New: Episode Payments for Cancer Therapy

Payer Management of Oncology Gets Serious

Unraveling the Complexity of Drug Shortages

Are We Winning the War on Cancer?

Putting Value Into Practice

Targeted Products Yield Most Promising Results

The Truth About Electronic Health Records

The Great Biomarker Chase

The 4 Pillars: Foundation for Care

Drug Profiles

Latest in Literature

The Economics of Cancer Care in the United States

Technologies Behind Biomarker Discovery and Development