As of March 2, 2012, there were 395,000 available apps for the Android phone, with 278,000 of those being free.

The iPhone has over 578,000 as of February 27, 2012, with 222,000 free.

The developers seem to have it figured out. I tend to pursue “free” apps only, but then find myself spending tens of dollars in fighting and avoiding advertisements. The $0.99 app of the same is likely free of such and therefore a valuable saver of time: the most precious resource. I also find it very ironic that even the “free” apps get reviewed and scored. It is very rare that we are asked to rate or score free items. Can you imagine driving down the interstate entering another state and suddenly being asked to evaluate the air— and not being able to leave the state or use an exit ramp until you do.

A recent evening snack also reminded me of another value “trick” that has befallen us: the beloved “half gallon” of ice cream that is no longer. The typical size of a carton of ice cream is now 1.75 quarts—a reduction of 1/8. When did that happen, and which rock have I been under? And it is not just ice cream. Candy bars, coffee, and toilet paper are further examples of lowering the quantity without lowering the price. The next evolution of these marketers is increasing the size with a greater than proportional price increase and calling it a “value size.”

Another example is the flood of commercials for gold, from “sell your grandmother’s gold to us for the best price” to celebrities telling how they have converted all of their assets to gold. I was perplexed with all of the sudden interest in these nuggets from the earth. It then dawned on me that all of this recent activity was created by the Gold Sellers Union in order to push up the demand for gold and thus increase the price. After all, isn’t there a limited supply of gold? When pondering the value of cancer care and how it is determined, I was struck by the difficulty of creating, defining, and promoting the value of quality cancer care. If we try learning from other industries, we should be able to do something like the following:

“Our cancer treatment was voted best by all cancer patients and their families. Use our free treatment or upgrade to our less-advertised version of treatment for only $10,000.” The advertisers would be subsidizing all of the treatments, free or not, and the subsidy would come from pharmaceutical companies, supply vendors, et cetera. Oooops, I forgot, this has already been determined to be illegal. Again, too much time for me under the rock.

Applying the above to our world, we could reduce the usual dose for specific cancer treatments, continue to promote that treatment, and then increase the dose to normal amounts and follow with promotions of “Value Dose.” Yep, you are right, not a good idea, and counterproductive to what we are here to do.

We do seem to have a real example of how increasing the demand does not necessarily increase the price. Consider the ongoing chemotherapy drug shortage issues. Most of current shortage drugs are generic, typically the least expensive in their class. Spontaneous increases in their costs, for regulatory or production reasons, are not matched with provider reimbursement due to the 6-month lag built into the ASP reimbursement system. This is an unexpected result of implementing unnatural forces into a world that is accustomed to natural market forces.

So why is it so hard to define, measure, and promote “value” in cancer care? My healthcare marketing professor said it best in describing the uniqueness of healthcare. It is one of the only industries where the consumer, decision maker, and purchaser are 3 different people. (This coming from the same professor that indicated Ferrero, the manufacturer of TicTacs, was actually selling “fun” and not breath mints.) The major stakeholders in our world are the patient (the consumer), the provider (the decision maker), and the payer (the purchaser). Each has their own list of priorities as well as their own subset of stakeholders. Upon close review, their priorities seem similar but not necessarily aligned.

Cancer patients are supported by their families, friends, and employers. According to a recent gathering of major stakeholders, the things patients desire from the care team include access, ability, affordability, affability, and availability. They also anticipate quality and timely communications, honesty, and the best possible outcome with the best possible quality of life. Additionally, they request the least amount of pain, toxicity, and test results.

Providers are not much different. They are surrounded by clinicians, advocate organizations, and networks of other providers and diagnostic facilities. They also want satisfied patients and families, best possible outcomes, minimized administrative burdens, a fair reimbursement for all of the services provided, and positive incentives to continue all of the above. Quality of life is paramount.

And are payers much different? It does not sound like it. Although they are accountable to their stockholders or taxpayers, they also desire similar outcomes. They want member satisfaction, the best possible clinical outcome, the highest quality care in the lowest cost setting, treatments for members that are cost-effective and evidence-based, and meaningful indicators of quality and value.

The common threads between these 3 major groups of cancer care stakeholders are patient and family satisfaction and measurable value. The challenge is to define these attributes so that they are measurable, relative, and aligned between all care providers and stakeholders. We do not have the luxury of being able to call on advertisement sponsorship, or to adjust the package size, or to artificially inflate demand—nor would we want to. So then, how do we become united in our efforts, definitions, and recognition?

The recent gathering of 16 representatives from the various stakeholder groups is a great start. These individuals have crossed competitive lines from their payer, provider, or group purchasing worlds to collaborate on solutions that will benefit the patients, their families, and one another. They recently met in Atlanta to collectively address this issue with collaborative, open, and honest communications. The goals are evident and obvious but the obstacles are real. Standardizing and measuring patient and family satisfaction is the simpler of the 2 and great strides have been made to implement and report this information across all specialties. However, the value proposition is much more difficult. One payer said it best—they cannot easily and arbitrarily pay a single provider group for higher quality or value. Everything has a cost, even in the above-mentioned scenarios. Our approach should be no tricks but instead transparent positive incentives to encourage, promote, and recognize quality and value. The industry leaders that were seated at the table on those 2 days believe that this can be accomplished and in a way that all stakeholders may benefit. Once the value proposition is defined, we will be able to redefine ageold payment systems so that all value and quality will be evident and rewarded. Are we there yet? Not yet, but if the same creative and passionate minds that are working on this issue were also involved in the ice cream decisions, we might still have a full half gallon of cookies and cream.

 From Strategic Practice Initiatives, Community Oncology Alliance, Washington, DC.

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; acquisition of data; analysis and interpretation of data; drafting of the manuscript; administrative, technical, or logistic support; and supervision.1. AppBrain website. http://www.appbrain.com/stats/. Accessed March 9, 2012.

2. 148Apps.Biz website. http://148apps.biz/appstore-metrics/. Accessed March 9, 2012.

Articles

Evidence-Based Oncology

Getting Smarter in How We Score and Promote Value

Cancer Care Value-Learning From Others

The rising cost of healthcare is a topic of constant discussion and equally constant consternation. A lot of money is spent on healthcare in America, far more than in any other Western country, and over time, there has been tremendous inflation in this spending, particularly when indexed against the GDP.

Oncology seems a particularly prominent passenger on this runaway train. Although oncology spending in both the commercial and Medicare sectors represents less than 10% of the total healthcare spend,

 several big-ticket items bring constant attention to this specialty. And why not, with immunotherapy costing $100,000 per course and oral targeted agents costing $5000 to $10,000 per month? These mind-boggling price tags seem out of reach for the average patient.

A major reason for the concern over the cost of these agents is the perceived lack of value. The clinical trials that have led to the approval of these agents often employ end points, or outcomes, that address only part of the value assessment patients must make. High cost may interfere with living longer or better regardless of disease-free survival or disease stability.

The ability to rank “relative values” associated with our therapeutic choices should empower us to make wise decisions in healthcare. It allows us to maximize value. And to the extent that we can improve outcomes, it allows us to improve quality of care. Since the healthcare dollar has finite limits, objective, evidence-based treatment should help us do better with the dollars available.

Sadly, ample evidence suggests we have far to go. The best marker of how far short we are falling is the regional variability in healthcare spend. Seniors in Minneapolis cost Medicare $3341 per year whereas in Miami, they cost Medicare $8881 per year, 2½ times as much.

 These variations are even more exaggerated when care during the last 6 months of life is analyzed. The data from the Dartmouth Atlas are most compelling.

Utilization of all healthcare services, including hospital days, ICU days, and doctors visits, goes up. But what is most alarming is the variability from state to state and from region to region. For example, hospital days in the last 6 months range from 7 in Utah and Oregon to almost 16 in DC and almost 12 in Florida. Office visits follow the same trends. Not unexpectedly, hospice enrollment follows an inverse relationship. Without question, socioeconomic factors explain some of the variability and there is no clear “quality standard” which allows definition of an appropriate benchmark. However, this much variability cannot be viewed as good.

This type of variability certainly occurs in oncology care, even on a much smaller scale. Our studies looking at charges for lung cancer therapy within a single large practice shows wide interphysician differences.

 Notably, spend was not correlated at all with better survival (

). Patients cared for by the most expensive doctors did just as well (or just as poorly) as those cared for by the most thrifty doctors. In oncology, the spend is spread among several services and even several sites of service. Although there are some publications based on Surveillance, Epidemiology, and End Results data in the Medicare population,

 there was very little in the published literature to guide us in identifying where opportunities lie. We therefore entered into a partnership with Milliman to study costs of cancer care in the commercial population.

The study analyzed data from Medstat 2007, a claims database of commercial insurers, including several BCBS plans, covering 28 million lives. We focused on the top 10 cancer diagnoses, which represented 70,000 individuals. Cancer was relatively uncommon in this cohort, only 0.7% of all covered individuals, but cancer claims made up almost 10% of the cost. The 10 cancer diagnoses represented about 65% of all cancer diagnoses in this cohort, with breast cancer being the most common diagnosis. Among the cancer patients, about 25% received chemotherapy in a given year. The average cost per cancer patient receiving chemotherapy was about $110,000 per year, 4 times as much as the average cancer patient not receiving chemotherapy. Further, the cost for cancer patients receiving chemotherapy was dramatically higher, more than 20-fold greater, than the cost for patients with other chronic diseases like diabetes.

So how is the money spent? The majority of the charges were for outpatient services (

). In analyzing the outpatient costs, only 25% of costs were for chemotherapy. The remainder of the costs included imaging, outpatient surgery, and other ambulatory services. We also found there were about 2 hospitalizations per year and 2 emergency department (ED) visits per year in chemotherapy-treated patients, half of which could be attributed to chemotherapy toxicity. Unfortunately, we found relatively low hospice utilization rates. And more concerning, we found a large cohort of patients who died in the hospital and received chemotherapy within 14 days of death.

As with the published experience with the Dartmouth Atlas, we identified marked regional variations in care (

). The range in chemotherapy costs was almost a third higher in the highutilizing regions, and not surprisingly, hospital admits and ED visits varied 2-fold and 4-fold respectively from lowto high-utilizing regions. This data set identifies opportunities for cost control, especially in chemotherapy costs, hospital and ED costs, and end-of-life costs.

The US Oncology Network has, for the last 6 years, focused on the ability to control costs by adopting an evidence- based treatment platform, Level I Pathways. These evidence-based treatment guidelines are embedded in the iKnowMed EHR and offered as a decision support tool, with reports that allow implementation of a process improvement methodology. We have reported on the impact of these evidence-based pathways in our network in patients with lung cancer and colorectal cancer.

Our first study, in non-small cell lung cancer patients, was a collaboration with Aetna.

 Over an 18-month period, we looked at cost of care in 1400 patients

at 8 sites in the US Oncology Network. Clinical data including stage of disease and line of therapy were documented. We studied chemotherapy costs as well as costs associated with acute care visits, E and M codes, laboratory, and supportive care drugs. Within our sites of service, 1100 of 1400 patients were treated according to guidelines, considered “on pathway,” and 300 of 1400 were treated “off pathway.” There was a substantial cost difference between the groups, with a 35% reduction in chemotherapy costs associated with being treated on pathway ($18,000 vs $27,700). Importantly, survival of those treated on pathway was identical to those treated off pathway (

We also analyzed the effect of pathways compliance in colon cancer.

 In this second study, we looked at costs associated with pathway status (on or off) in a national database with the assistance of Milliman. Since survival data were not available in this claims system, we analyzed survival with respect to pathways status within iKnowMed. We again found a substantial savings associated with being “on pathway,” about 35%. Interestingly, we found evidence that disease-free survival and overall survival with treatment on pathway were at least as good as in the offpathway cohort. A preliminary review of inpatient charges and hospitalization rates within the on pathway/off pathway cohorts suggests reduced costs and utilization in the on-pathway group, providing further evidence of cost savings associated with adherence to these evidence-based treatment guidelines.

This body of data makes a compelling case for value associated with a disciplined, cost-conscious, evidence-based approach to chemotherapy decision making. This value derives from clearly reduced costs but also improved outcomes. The value associated with this approach is physician developed and driven. And a similar physician developed and driven approach may well be feasible to attack costs associated with hospitalizations and ED visits and especially end-of-life care, where there is ample opportunity for improvement.

There are clearly challenges to the broad adoption of this approach. First, there are innumerable evidence-based treatment guidelines. Most of these are at best cost neutral and at worst cost insensitive. It would be a mistake to assume an equal benefit across all of these guidelines. Second, this approach requires a genuine attempt at process improvement. Reporting and accountability are mandatory. Without physician buy-in, the process is doomed to failure. Finally, there is widespread dissatisfaction with the current oncology reimbursement methodology. A transition to a methodology that financially rewards high-level, quantifiable performance will greatly enhance likelihood of general acceptance. There will need to be trust between payers and providers to succeed in this system. Ultimately, the reward will be improved value and enhanced quality.

From New York Oncology Hematology and Albany Cancer Center (MK), Albany NY; Texas Oncology (JRH), Austin, TX; and US Oncology (MK, JRH), Houston, TX.

Drs Kolodziej and Hoverman report employment with US Oncology, Houston, TX.

 Concept and design (MK, JRH); acquisition of data (MK); analysis and interpretation of data (MK, JRH); drafting of the manuscript (MK, JRH); critical revision of the manuscript for important intellectual content (MK, JRH); provision of study materials or patients (MK); and supervision (MK).1. Borger C, Smith S, Truffer C, et al. Health spending projections through 2015: changes on the horizon. Health Aff (Millwood). 2006;25:w61- w73.

2. Tangka FK, Trogdon JG, Richardson LC, Howard D, Sabatino SA, Finkelstein EA. Cancer treatment cost in the United States: has the burden shifted over time? Cancer. 2010;116(14):3477-3484.

3. Congressional Budget Office. Geographic Variation in Healthcare Spending 2005. www.cbo.gov/ftpdocs/89xx/doc8972/2-15-GeogHealth.pdf.

4. The Trustees of Dartmouth College. The Dartmouth Atlas of Health Care. http://www.dartmouthatlas.org/.

5. Hoverman JR, Robertson SM. Lung cancer: a cost and outcome study based on physician practice patterns. Dis Manag. 2004;7:112-123.

6. Hassett MJ, Neville BA, Weeks JC. The relationship between cost, quality, and outcomes among women with breast cancer in SEER-Medicare. J Clin Oncol. 2011;29:384S(suppl; abstr 6001).

7. Kolodziej M, Hoverman JR, Garey JS, et al. Benchmarks for value in cancer care: an analysis of a large commercial population. J Oncol Pract. 2011;7(5):301-306.

8. Neubauer MA, Hoverman JR, Kolodziej M, et al. Cost-effectiveness of evidence-based treatment guidelines for the treatment of non-small-cell lung cancer in the community setting. J Oncol Pract. 2010;6(1):12-18.

9. Hoverman JR, Cartwright TH, Patt DA, et al. Pathways, outcomes, and costs in colon cancer: retrospective evaluations in two distinct databases. J Oncol Pract. 2011;7(3)(suppl 3):52s-59s.

Value-Based Reimbursement in Oncology 

Recent studies offer new insights into ALK detection methods and related treatments. Screening for the non-small cell lung cancer (NSCLC) subtype has been at the forefront of NSCLC research, and numerous published studies have established meaningful results spanning a vast spectrum of testing approaches. While fluorescence in situ hybridization (FISH) has been the “gold standard” of detecting ALK gene rearrangement, several clinical trials evince limitations in this method—in terms of both cost and effectiveness&mdash;and oncologists and other medical professionals suggest administering a combination of screening methods to adequately identify ALK-positive NSCLC. The US Food and Drug Administration (FDA) has recently approved FISH as the sole testing method for ALK gene rearrangement. Further, it is also the prescreening step for ALK treatment eligibility. Crizotinib (Xalkori), an orally taken ALK inhibitor, is currently the only FDA-approved drug treatment for ALK non-small cell lung cancer, and since its prescription is entirely contingent upon positive FISH results, many researchers promote the standardization of other screening methods, which could be more accurate and cost efficient. Many payers, however, argue that the efficacy of FISH is enough to validate its usage, and that this current trend of companion diagnostic devices will, in the long run, promote more efficient use of treatment and better patient outcomes.

Anaplastic lymphoma kinase, or ALK, is a subset of non-small lung cancer that represents about 4% of lung adenocarcinomas.

 This subset was discovered in a 2007 Japanese study that identified “a fusion gene comprising portions of the echinoderm microtubuleassociated protein-like (EML4) gene and the anaplastic lymphoma kinase (ALK) gene….”

 Interestingly, ALK rearrangement is almost exclusively found in non-smokers, or light smokers (less than 10 packs a year). Further, researchers have identified at least 13 known variants of the EML4-ALK fusion gene, a characteristic often cited as diagnostically problematic, especially given the rareness of ALK rearrangement.

In August 2011, the FDA approved the oral ALK inhibitor crizotinib (licensed by Pfizer under the brand name Xalkori), and it is currently considered the standard method of treatment for ALKpositive NSCLC. Prescription, though, is contingent upon the testing for and subsequent positive identification of ALK rearrangement. To meet this requirement, the FDA approved Abbott Laboratories’ Vysis Break Apart FISH Probe Kit as the sole companion test to crizotinib treatment. This test-treatment combination is part of the larger trend of personalized medicine development, and it represents what Jenifer Antonacci, director of media relations, Pfizer Inc, calls “a shift away from a one-size-fits-all approach, toward biomarker-based treatment decisions.” But with FISH’s high up-front costs and wavering results, many still question the viability of offering the FISH kit as the sole screening method for NSCLC patients.

Testing for and Treatment of ALK-Positive Non-Small Cell Lung Cancer

FISH continues its reputation as the “gold standard” for ALK screening. Being the only FDA-approved companion diagnostic test to crizotinib treatment, its diagnostic merit and cost are sources of much controversy among medical professionals. The test’s diagnostic challenges are often cited in the literature. For instance, a 2011 multi-institutional study by Paik et al reported that out of 735 NSCLC patients, FISH identified ALK-gene rearrangement in only 28 patients (3.8%), while immunohistochemistry (another ALK testing method currently under evaluation) identified 55 patients (7.5%) as ALK positive.

More important, FISH is an expensive procedure, its steep cost further compounded by laboratory fees. A 2011 Forbes article prices a FISH test at ~$1500, which includes the cost of the test (~$250) and pathology services.

 Further, because Abbott’s FISH kit is biomarker-based (the Vysis FISH kit is optimized to locate only ALK gene mutations), it supposes a potential waste of resources; the same Forbes article finds that only 1 out of 25 ALK-tested patients actually test positive for ALK gene rearrangement. As a result, oncologists and subspecialists are working to standardize a more diagnostically effective and economical method for ALK screening. When asked about the economic implications of FISH, Joanne E. Yi, MD, anatomic pathology and clinical pathology, Mayo Clinic, had this to offer: “Most community pathology laboratories do not have the equipment or personnel to perform this test, and they usually send out to reference laboratories. FISH probe for ALK translocation in a lung cancer setting is now more expensive since the FDA approved the drug with the (FISH) companion test…the prevalence of ALK translocation is so low, and if you do cost analysis it (alternative testing and treatment) will be still much cheaper even if you reflex to more FISH.”

Nonetheless, proponents of FISH cite the method’s newly improved assays and ability to positively identify ALK translocation without further validation by other diagnostics as acceptable reasons for its standardization.1 Many also propose administering a combination of screening methods should FISH produce a false negative.

Health plan professionals, as well, are championing the apparent success of companion diagnostic devices like FISH. They argue that the potential effectiveness of a biomarker-based test like FISH outweighs its high cost, and that as a prescreening step before treatment, it enables payers and patients to avoid much higher expenditures on what would be unnecessary treatment.

Crizotinib (Xalkori) was approved by the FDA in August 2011, and is targeted therapy for the treatment of ALK-positive NSCLC. Responses to the drug have been mostly favorable, with the results of the initial drug trials showing a 57% response rate after just 8 weeks of treatment.

 While adverse effects have been reported, all are relatively mild, with the most severe being temporary visual impairment (

Much like its companion FISH test, however, crizotinib comes with a high cost. In 2011, Emaxhealth.com reported that crizotinib costs approximately $9600 a month, and with its reliance on the FISH probe kit as a companion test, the total cost of ALK screening and treatment would be “prohibitive for many.”

In an effort to make crizotinib more affordable and accessible, Pfizer is offering a copay assistance program that enables privately insured, eligible patients to pay no more than $100 per prescription.

 It is important to note, though, that both the drug and copay assistance are only available at participating specialty pharmacies. The company is also offering its First Resource counselors to help uninsured or ineligible patients find other crizotinibgranting assistance programs.

Additionally, other treatments for ALK-positive NSCLC are currently under evaluation. A recent study identified 18 ALK-positive patients with an acquired resistance to crizotinib.

 Recent papers have noted the efficacy of pemetrexedbased therapies

 and ganetespib (a heat shock protein 90 inhibitor)

Will the current trend of personalized medicine ultimately engender a future of improved healthcare? In a recent interview, 

, Clinical Policy Research & Development, Aetna, discussed the impact of ALK testing and other companion diagnostics on policy making and patient outcomes:

Does Aetna currently cover the costs of both FISH testing and crizotinib treatment?

This is an interesting treatment, because you have an oral medication that’s covered under your pharmacy benefits, and then you have a companion diagnostic that would be covered under medical benefits. Yes, we would cover both for their approved indications at this time.

Do you see other health plans jumping on board with offering both of these recently FDA -approved components?

 I think that you’re going to see pretty uniform coverage for the test and the treatment. It is an FDA-approved treatment for cancer. I believe the National Comprehensive Cancer Network has (also) endorsed the use of this for the treatment of people with NSCLC…. To ensure that the product is working appropriately, you would cover, under the medical benefits, the FISH test that’s used.

To what extent does the cost of FISH factor into your coverage decisions?

This is an important point—we make the coverage decision based on the evidence of effectiveness. The cost-effectiveness is factored into the coverage decision only after you’ve made the coverage decision….Aetna has agreed to cover cancer drugs with indications that are recognized by the NCCN of level II/B or greater. So in addition to FDA approvals, the NCCN guidelines are factored into our coverage decision.

 So with research indicating that only 1 out of 20 or 25 patients will actually test positive for ALK gene rearrangement, do you find covering the costs of FISH is in any way a waste of resources? Is it problematic?

The nice part about this (FISH) test is that it allows you to focus on the 1 out of 20 patients that would actually benefit from this (Xalkori) drug. It actually allows for more efficient use of resources. Also, the drug has adverse effects, some that are potentially serious. So in using this test, you’re able to focus the use of the drug on the people that benefit, and not expose the 19 out of 20 patients who will not benefit, from the risks, including the adverse reactions, by exposure to this drug.

Pfizer is currently offering the Xalkori drug in conjunction with a $100 copay assistance program for underinsured patients whose health plans do not offer coverage. Do you think it is in these patients’ best interest to pay out of pocket for the FISH test?

 Yes. It (the cost of FISH) is minimal to the cost of the drug. You would want to know if you’re 1 out of 20.

 A stipulation of that Pfizer program is that it only allows a maximum annual savings of $24,000, which is approximately 2 months’ worth of treatment. Isn’t this an inadequate amount of treatment for the average ALK-positive patient? What does the underinsured patient do in this scenario?

Yes. The average patient is on the drug for about 10 to 11 months…But I imagine that the program is allowing coverage with the idea that in the meantime, the patient will be getting coverage, or getting on Medicaid, or some other arrangement where they will get coverage for continued treatment.

Both Abbott’s FISH kit and Pfizer’s Xalkori represent a recent breakthrough in personalized cancer treatment. Do you foresee an emergence of potential competitors?

Not so much competitors. What I see is that this is a trend. The idea of having tests that determine whether someone should be eligible for certain treatments…I think in the future we’re going to see many more examples of drugs that are developed in tandem with diagnostic tests, or also the development of diagnostic tests after drugs come out. I think you will see both. The idea is that you can focus treatment on the subgroup of patients who would benefit the most.

So, to conclude, you view this trend of personalized medicine as beneficial to patient outcomes overall?

I think it will benefit patient outcomes, and also lead to a more efficient use of resources…The development of these companion diagnostics is essential to be able to demonstrate the benefits of a specific therapy, especially a specific therapy that only benefits a small subgroup of patients with a particular condition. So I do think we’re going to see more development of these companion diagnostic devices. In fact, the FDA has offered some direct guidance for industry on the development of these companion diagnostics, so it’s definitely going to be a trend in the future.

 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.

Signaling the Future of Personalized Medicine

Testing for ALK-Positive NSCLC

Prostate cancer is the most prevalent non-cutaneous malignancy among men, accounting for over 240,000 new diagnoses each year in the United States.

 Because of its indolent nature and the excellent curative options for early-stage disease, prostate cancer deaths are more modest, occurring in fewer than 34,000 men each year.

According to estimates from the American Cancer Society, the 5-year survival for patients with prostate cancer is almost 100%, and the 10-year survival is 91%.

In a significant portion of patients, prostate cancer progresses very slowly or poses limited danger. Therefore, it is sometimes said that “more people die with prostate cancer than of prostate cancer.” Conservative approaches to treatment for patients with indolent prostate disease often include little more than periodic monitoring with prostate-specific antigen (PSA) testing.

Even patients with indolent prostate cancer often choose active treatment approaches, which can include surgery or radiation therapy followed by hormonal therapy, which essentially reduces testosterone to post-castration levels. In patients with active disease, this approach prolongs survival, but in a proportion of these patients, the disease will progress. Once patients reach this advanced stage, called metastatic castrate-resistant prostate cancer (CRPC), the disease is no longer indolent, having a median survival of only 16 to 20 months.

 For these patients and the healthcare system, the question of value is more of a consideration.

Nearly 2.36 million American men are estimated to have prostate cancer,

 and the total cost of caring for these patients has been estimated to be $9.86 billion.

 Approximately 10% to 20% of these men will develop CRPC within 5 years of diagnosis.

 In 1 health economic study of CRPC patients, the total per patient prostate cancer—related costs were $21,588 annually.8 In another study, performed in 2006 prior to the approval of the 4 most recent agents, the mean costs for the last year of life were $33,691.

 Current costs are almost certainly significantly greater.

For patients who have metastatic CRPC, metastases are most often found in the bone, with 1 study reporting that 84% of all patients with CRPC have bone metastases upon diagnosis.

 These patients generally receive either the bisphosphonate zoledronic acid or the more recently approved targeted agent denosumab to prevent or delay skeletalrelated events (SREs) associated with bone metastases.

 Radiation therapy may also be used to control bone pain, and surgical intervention is sometimes necessary as well. In addition to these palliative treatments, the active treatments described below are prescribed, depending on whether these patients are currently experiencing symptoms or not.

For asymptomatic metastatic CRPC patients, the National Comprehensive Cancer Network recommends treatment with 1 course (3 doses) of sipuleucel- T (Provenge),

 the first therapeutic vaccine to be approved by the US Food and Drug Administration (FDA) and which has been shown to produce a survival advantage of 4.1 months.

 Asymptomatic patients are also often treated with secondary hormonal therapy, such as ketoconazole or an antiandrogen, although no survival benefit has ever been established for this approach.

Once patients develop symptomatic disease, they generally receive treatment with the chemotherapeutic agent docetaxel (Taxotere), which has demonstrated a survival advantage of 2.4 months.

After failure of docetaxel, several options exist, including (1) the targeted hormonal agent abiraterone acetate (Zytiga), providing a survival benefit of 3.9 months,

 (2) another chemotherapy agent, cabazitaxel (Jevtana), providing a survival benefit of 2.4 months,

(3) docetaxel rechallenge, and (4) secondary hormonal therapy.

All of the above-outlined, recently approved treatment options for CRPC patients come at a high price tag. Sipuleucel- T is the most expensive therapy, costing $93,000 for a full course, but only 1 course of therapy is given to each patient. The average wholesale price of cabazitaxel is $9600 for 1 course of treatment, with a median of 6 courses given in the pivotal trial, for a median total of $57,600 per patient.

 Abiraterone costs $5000 per month and the average duration of treatment in its pivotal trial was 8 months, for an average total of $40,000 per patient.

Abiraterone has the additional challenge of being an oral drug, which is often covered (or not covered) under a patient’s pharmacy benefit rather than as a medical benefit. Because prescription drug coverage is typically less generous than medical coverage, patients prescribed oral targeted agents often find themselves responsible for paying thousands of dollars in coinsurance. Thus, the amount of patient out-ofpocket costs often becomes the deciding factor in treatment choice, with patients often forgoing life-prolonging therapy due to the high cost of the drug.

For the prevention of SREs, the cost of denosumab is $1650 per dose, compared with $844 for zoledronic acid,

 but the drug acquisition costs are not the only considerations when determining overall cost-effectiveness. Because denosumab is administered via subcutaneous injection rather than intravenous infusion, it saves both chair time and infusion costs relative to zoledronic acid. In addition, denosumab avoids 0.11 SREs per year in patients with CRPC.

In 1 health economic study, when all costs were considered, including the cost of avoided SREs, denosumab was associated with a $51,319 incremental increase per SRE avoided over a 3-year period in this patient population.

 Based on a willingness-to-pay threshold of $70,000 per SRE avoided, denosumab was costeffective in nearly 50% of cases at 1 year and 79% of cases at 3 years.

According to 1 analysis, costs incurred by patients with CRPC are greatest in the 6 months preceding death because of home-care services, hospitalization, and palliative-care costs.

 This analysis was conducted before the advent of the newer, more expensive drugs now available for the treatment of CRPC. In the current landscape, drug costs are certain to be a formidable driver of costs. However, unlike many therapies in the past, these drugs produce a survival advantage, making them potentially a good value despite their high cost.

In a recently published health economic study of patients with prostate cancer, ambulatory costs were determined to be the main driver of the cost of care, accounting for 57% of the total costs.8 Ambulatory costs were those incurred during physician office visits and visits at outpatient facilities, such as outpatient procedures and services (eg, laboratory work, radiology services). The next most costly driver of the cost of care for patients with CRPC was inpatient costs, absorbing 30% of the total costs. Pharmacy costs accounted for less than 10% of the total cost, and emergency department costs were negligible.

Prostate cancer is a bit unusual as a carcinoma because it is either aggressive or very slow growing and there are a number of options to treat it (eg, surgical resection, cryotherapy, radiologic therapy, chemotherapy, immunomodulatory treatment). How do health plan efforts to help patients make choices that are most appropriate for them provide value?

Helping patients make the choice that is right for them is a challenge because of the fragmented nature of the sites of care for prostate cancer. Urologists attempt to provide counseling but their bias is to do surgery, and patients may be unintentionally steered in that direction. Patients themselves let their own biases choose therapies. For example, they may decide on proton-beam therapy, based on marketing, rather than other forms of radiation therapy, which are equally efficacious but much less costly.

Our health plan is embarking on “shared decision-making” pilots around this area, in an effort to help patients objectively wade through the volume of information on the various treatment modalities in an objective and organized manner free of individual provider or marketing biases. These shared decision-making tools will be available at both specialty care sites and primary care offices for patients diagnosed with prostate cancer and working through the decision process as to how they wish to proceed with treatment.

What is your view on prostate-specific antigen (PSA ) testing and its ability to stratify patients at risk for aggressive malignancy?

The role of PSA testing has become more controversial, given the recent recommendations of the US Preventive Services Task Force to discontinue use of this test as a means to screen for prostate cancer. This recommendation was based upon their review of a number of studies but especially 2 large studies that showed the harms from this testing likely outweighed the benefits.

This recommendation has not been universally supported by urologists and some other practitioners, as they feel PSA testing has some benefit when used in conjunction with a digital rectal exam of the prostate and when viewed serially over time rather than as a single value.

From a payer perspective, I believe there is increased skepticism regarding the value of PSA testing as it is primarily being performed by primary care physicians (PCPs) and they remain for the most part uninformed about the nuances of this testing. There is a great deal of evidence to support that PSA testing is not a sensitive tool for determining the aggressiveness of prostate cancer, but at the same time it is a readily available and accepted test by PCPs and thus is used.

How strong a role does your organization’s medical technology assessment group play in policy making for prostate cancer treatments (versus a Pharmacy & Therapeutics [P&T] Committee)?

It depends on the treatment. Drugs are typically assessed by a P&T Committee whereas other treatments like surgical procedures, radiation, or cryotherapy are evaluated by the Technology Assessment Committee. There can be some overlap in committee function should there be a pharmaceutical treatment that is administered by some unique device. In that circumstance, the technology assessment committee would take the lead and present its final determination to P&T for notification and discussion.

Does your health plan cover the Provenge vaccine?

We do cover Provenge, but we apply prior authorization that is specific to the FDA labeling.

Do you believe that therapeutic vaccines like Provenge will provide an avenue to good value in prostate cancer treatment?

Therapeutic vaccines have the potential to offer an alternative treatment for patients who have failed alternative therapies and perhaps over time an earlier line of therapy. However, the word “value” is pejorative. Is this clinical “value” or financial “value”? At the current price points set for Provenge, it doesn’t seem to offer significant financial value, though it may offer limited clinical value. The failure of urologists and medical oncologists to embrace this therapy as evidenced by its slow update may also speak to residual questions regarding the clinical value of this particular therapy, but I don’t think it is a statement regarding therapeutic vaccinations in general.

From a health plan perspective, Provenge is not felt to be of value based on its current pricing and the fact that it offers limited clinical benefit based on current clinical studies.

What do you believe is the most exciting area for pipeline research in prostate cancer?

Immune system modulation—whether it be through therapeutic vaccine or biologic therapy&mdash;is the area that has the greatest “mojo” at present. Given that for many patients, prostate cancer is an indolent disease that has characteristics which are more akin to a chronic immune state like lupus, rheumatoid arthritis, or multiple sclerosis, engaging a targeted approach that helps the immune system identify and eliminate aberrant cell lines shows significant promise in treating this condition.

Dr Schaecher is medical director, SelectHealth, based in Salt Lake City, Utah.

Stokes ME, Ishak J, Proskorovsky I, Black LK, Huang Y. Lifetime economic burden of prostate cancer.

Prostate Cancer

The 29th Annual Miami Breast Cancer Conference culminated in a thought-stirring last session. J. Michael Dixon, MBChB, MD, professor of surgery at the University of Edinburgh and clinical director of the Edinburgh Breast Unit at the Western General Hospital,Edinburgh, Scotland, and Patrick I. Borgen, MD, director of the Brooklyn Breast Cancer Program at Maimonides Breast Cancer Center in Brooklyn, New York, debated the pros and cons of longterm clinical follow-up care of patients with breast cancer.

The Con Argument: Clinical Exams Increase Costs and Psychological Distress

“It is always difficult to give up something that you are used to doing,” began Dixon’s argument against frequent follow-up for breast cancer patients in remission. “There are numerous guidelines but very little guidance,” he said, highlighting the disparity in follow-up guidance in different parts of the world. Currently, North American guidelines suggest that clinical examinations take place every 3 to 6 months for the first 3 years, every 6 to 12 months for the next 4 to 5 years, and on an annual basis thereafter for women in remission from breast cancer.

Dixon challenged the notion that intense follow-ups improve outcomes for women previously treated for breast cancer. He highlighted studies that have looked at the detection of systemic recurrence in women previously diagnosed and treated for breast cancer.

A 1994 randomized study comparingpatients undergoing intensive laboratory and x-ray—based follow-up assessments to standard of care found more metastases earlier in the intensely followed group—but at the expense of significant false-positive rates.

 Dixon concluded that because the 5- and 10-year data analysis did not show any differences in overall survival in the 2 trial arms, the intense follow-up was not cost-effective.

A 1999 study compared the 10-year mortality rates in women who had undergone treatment for primary breast cancer. The women had either intense or standard clinical follow-up.

 The more intense protocol did not offer a survival advantage, the study concluded.

A more recent analysis from 2007 showed that traditional routine clinical checkups were not sufficient enough to prevent disease recurrence, questioning the need for frequent follow-ups.

 The study authors stated that alternative follow-up methods were acceptable for patients, as these did not decrease either quality of life or anxiety about recurrence. Less-frequent visits can, however, offer significantly lower costs and time savings.

“Just because you can, doesn’t mean you should,” Dixon stressed, pointing out that recurrent clinical follow-ups resulted not only in unnecessarily increased healthcare costs, but also in creating psychological distress that can negatively affect the health of a patient.

Dixon’s solution? More effective ways of achieving improved patient outcomes with minimal psychological stress by seeing regular physiotherapists or nurses, rather than undergoing regular clinical follow-up assessments.

Dixon discussed a recent United Kingdom study that followed a total of 32,877 women from the West Midlands Cancer Intelligence Unit Cancer registry; 18,706 of the included women had breast conservation surgery, and 15,171 had mastectomies following a breast cancer diagnosis. Analyses showed that earlier detection generally led to better outcomes. The study also showed that clinically detected recurrences did worse compared with detection via mammography or by the patient herself. Overall survival was very much dependent on the size of the second tumor detected. The aim should be to detect recurrence as early as possible, Dixon concluded.

How much does follow-up cost? Dixon discussed an economic model, in British pounds, that incorporated different treatment regimens, the estimated likely survival benefit per regimen, and the cost per incremental quality-adjusted life-years (QALYs), among other metrics, for a woman aged 57 years. The utilization of extra tests such as mammography, clinical examination, and magnetic resonance imaging (MRI) did not lead to added benefit, except for younger women. The top 3 most cost-effective options were mammography, followed by clinical examination and mammography, and clinical examination and an MRI.

“Current clinical follow-up programs waste time and resources,” Dixon said. They are much better off targeting specific groups that have clinical issues, he concluded. “Local recurrence rates are falling. Therefore, the cost detection of each recurrence is increasing.”

The Pro Argument: Patient Care Is Personal

Borgen’s pro argument emphasized the soft side of the physician-patient relationship and the fundamental goal of patient follow-up—peace of mind and regular surveillance to catch recurrence as early as possible. Borgen believes that there is a survival benefit of patients seeing their oncologist regularly.

Borgen stated that he was surprised at the seemingly high rate of clinically detected first recurrences, 13.5%, cited by Dixon. “My guess is that the rate is actually far lower than this,” he commented.

Borgen discussed the subjective perspective of the relationship between the physician and the cancer patient,emphasizing the relationship of the patient

with the surgeon as the first point of contact and a help in “navigating the maze of diagnostic and treatment options.” Borgen said he believes that patients often are reassured by staying in close contact with their surgeon as a “source of information.”

From a physician’s perspective, the benefit of following a breast cancer patient in the long term is training. Longterm follow-up can be highly valuable for residents and physicians early in their careers. Understanding the longterm effects of surgery and therapy help better train surgeons and oncologists, argued Borgen.

Borgen concluded with something that hits home for most clinicians (and patients): the personal aspect of care. “It’s always problematic to apply national, aggregate numbers to the patient that is sitting in front of you,” he said. “The only way to really achieve what Dr Dixon discussed is a policy change in the [United States]. That policy change would likely be driven by insurance payers who would simply refuse to pay for follow-up care.”

Is this the future in the United States? Not without relevant, convincing, largescale patient follow-up data.

Concept and design; drafting of the manuscript; and critical revision of the manuscript for important intellectual content.1. Del Turco MR, Palli D, Cariddi A, Ciatto S, Pacini P, Distante V. Intensive diagnostic followup after treatment of primary breast cancer: a randomized trial. JAMA. 1994;271(20):1593- 1597.

2. Palli D, Russo A, Saieva C, et al. Letter to the editor. Intensive vs clinical follow-up after treatment of primary breast cancer: 10-year update of a randomized trial. JAMA. 1999;281(17):1586.

3. Montgomery DA, Krupa K, Cooke TG. Alternative methods of follow up in breast cancer: a systematic review of the literature. Br J Cancer. 2007;96:1625-1632.

Long-Term Breast Cancer Patient Follow-Up Care 

Myeloproliferative disorders are associated with bone marrow malfunction. The bone marrow contains stem cells that develop into red blood cells, white blood cells, and platelets in appropriate proportion. A change in the DNA of a single stem cell causes a growth advantage for one of the cell types, which leads to an abnormal under- or over-production of the respective cell types.

Polycythemia vera, essential thrombocythemia, and primary myelofibrosis together comprise the myeloproliferative neoplasms, which are considered Philadelphia- chromosome—negative chronic myeloproliferative neoplasms.

Polycythemia vera is characterized by an excessive amount of red blood cells being formed by the bone marrow. There may also be an increased number of leukocytes (white blood cells) and platelets and an enlarged spleen. Essential thrombocythemia is the result of the overproduction of platelets. As either of these 2 disorders progresses, bone marrow scarring may occur, which leads to myelofibrosis. Polycythemia vera progresses to myelofibrosis in about 15% of the cases, while only a small number of patients with essential thrombocythemia progress to myelofibrosis.

 Myelofibrosis can also arise without pre-existing conditions. Primary myelofibrosis and myelofibrosis secondary to polycythemia vera and essential thrombocythemia have a common mutant allele— JAK2.5 About 50% of patients with essential thrombocythemia have this same gene mutation as well as 95% of patients with polycythemia vera.

Each of these diseases typically occurs in the fifth or sixth decade of life. Patients with essential thrombocythemia can lead a normal life with an unaffected life expectancy. The median survival for polycythemia vera is more than 10 years with treatment. Myelofibrosis has the worst prognosis of the 3 diseases, as it has a median survival of less than 3 years but younger patients (<55 years) have survivals of more than 10 years.

 Patients are stratified by risk (low risk, intermediate-1, intermediate- 2, or high risk) based on patients’ number of risk factors, which is predictive for survival.

Approximately 10% to 20% of patients with myelofibrosis progress to acute myelogenous leukemia.

Treatment is guided by addressing the presenting risk factors, with the goal of extending survival.

 Based on few effective treatments (and the relative rarity of these cancers), evidence for the economic value of treatment has not yet been quantified.

Polycythemia, essential thrombocythemia, and myelofibrosis are classified as orphan diseases, as they affect fewer than 200,000 people in the United States at any given time. Currently, these diseases are not measured by the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. Market research has estimated that all 3 diseases have an annual incidence of fewer than 3 patients per 100,000 population.

 In 2003, the prevalence of polycythemia vera was 22 per 100,000 (65,243 patients total), and the prevalence of essential thrombocythemia was 24 per 100,000 (71,078 patients).

 Researchers investigating myelofibrosis in 1999 reported an incidence of 1.46 per 100,000, with a total prevalence of 30,000 patients.

It is therefore understandable that for most health plans, these myeloproliferative neoplasms do not merit intense scrutiny. However, the available treatments for these disorders vary quite dramatically, and the therapeutic options for myelofibrosis in particular have changed dramatically in the past year.

Patients without symptoms or with minimal symptoms are usually managed with a watch-and-wait strategy, until the patient’s risk score worsens or hematological abnormalities necessitate intervention.

Therapies for polycythemia vera and essential thrombocythemia are similar, including phlebotomy to reduce the number of circulating red blood cells, low-dose aspirin to reduce the chance for blood clots (and to alleviate vasomotor symptoms experienced by some patients), hydroxyurea and anagrelide for those at high risk for blood clots, and interferon. Hydroxyurea is also used to treat splenomegaly, a complication of these disorders.

Until late 2011, there were no approved therapies for myelofibrosis. Off-label therapies employed included hydroxyurea, androgens, corticosteroids, erythropoiesis- stimulating agents, danazol, thalidomide, lenalidomide, busulfan, melphalan, cladribine, and interferon. Blood transfusions, radiation, and removal of the spleen have been tried as well. However, these therapies have not prolonged survival.

 The only known cure for myelofibrosis has been allogeneic hemopoietic stem-cell transplantation, which is itself associated with high morbidity and mortality as well as high costs.

Ruxolitinib (Jakafi), an oral JAK1 and JAK2 kinase inhibitor, was approved in November 2011 for the treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post—polycythemia vera myelofibrosis, and post–essential thrombocythemia myelofibrosis.

 Two phase III trials demonstrated significant improvement compared with best available therapy for spleen size, symptoms, and burden reduction, as well as for quality of life.

However, the reduced spleen size was not shown to be consistently durable in a phase I/II study and neither phase III study reported a significant survival benefit.

 This agent is commonly associated with hematologic side effects; anemia was reported in 96% of patients taking ruxolitinib (grade 3/4, 45%), and thrombocytopenia was reported in 70% (grade 3/4, 13%).

This first JAK inhibitor therapy for myelofibrosis has been long anticipated; yet, the value of this treatment is not truly known. The treatment of adverse events and its overall effect in avoidance of other therapies will need to be included in the value equation. It is likely that it will be covered by health plans because of the low incidence of the disorder and the lack of other effective treatments.

Until recently, very little information was available about the costs of myeloproliferative neoplasms. A study presented at the American Society of Hematology meeting in December 2011 showed that annual medical and drug costs for patients with myelofibrosis neoplasms were 2 to 6 times that of patients with ailments other than cancer.

This study tracked the costs of 25,145 patients with these disorders, based on claims from a database of about 100 payers across the country.

For patients with myelofibrosis, mean total annual costs were $34,690, with outpatient costs accounting for 53% of the total (mean, $18,395). Inpatient visits (23%, $8106), drug costs (22%, $7803), and emergency department visits (1%, $386) accounted for the remaining costs. Patients with myelofibrosis incurred the greatest costs, followed by patients with essential thrombocythemia (mean annual total, $19,672) and polycythemia vera (mean annual total, $11,927).

May

Cancer Care Value-Learning From Others

Value-Based Reimbursement in Oncology

Testing for ALK-Positive NSCLC

Prostate Cancer

Long-Term Breast Cancer Patient Follow-Up Care

Myeloproliferative Disorders and Myelofibrosis

BRCA1/2 Genetic Testing Found Cost-Effective in Current Era

Trends in the 2012 Eisai Oncology Digest: Patient Demographics and Cancer Treatment Goals

Literature Review

On the Horizon for Multiple Myeloma

Oncology Hit Hard by SGR Debacle

Forging a Pathway to Quality Cancer Care

Is Provenge Angst a Symbol or Symptom of the Times?

Chronic Myelogenous Leukemia