With 180 oncologists practicing at more than 30 locations, UPMC Cancer Centers is one of the largest networks of cancer specialists in the country. In the early 2000s, the oncologists at UPMC recognized the importance of consistency and quality of care and the difficulties of ensuring a uniform level of care across their large distributed network. At the same time, they found themselves caught in the crosshairs of healthcare plans’ efforts to ratchet down the rising costs of cancer care. Together, these factors drove UPMC oncologists to develop clinical cancer pathways. Clinical pathways are treatment plans that lead physicians to 1 preferred treatment for a given state and stage of disease.

 Pathway programs are believed to be a cost-effective way to provide evidence-based patient care.

Over the past several years, UPMC has continued to use, improve, and expand its pathway program. For UPMC, clinical pathways are a way to ensure that all patients going to any UPMC location get the same care.

Prompted by its success and a growing interest in pathways among the broader oncology community, UPMC commercialized its program. This move made its well-founded pathways, now known as Via Oncology Pathways, available to practices across the United States and internationally. To date, UPMC is the biggest customer of the commercial pathway service. The added contributions of external practices on the pathways committees are considered a valuable commodity, according to Kathy Lokay, president and chief executive officer of D3 Oncology Solutions, the UPMC affiliate that now owns and operates the Via Oncology Pathways. To date, practices in 11 states, India, and Ireland have purchased the Via Oncology Pathways, with many more in active discussions.

Peter Ellis, MD, director, Medical Oncology Network of UPMC Cancer Centers, explained that commercialization allows UPMC to leverage costs to expand the pathways to more cancer types, more modalities of care, and more phases of care. The pathway program, which initially focused on chemotherapy protocols for 3 or 4 diseases, has grown to include 95 percent of cancer incidences and now supports decisions surrounding prognostic testing, imaging, radiation therapy, and supportive care. In 2011, pathways were launched for gastric cancer, bladder cancer, and chronic myelogenous leukemia. The group plans to roll out a testicular cancer pathway this year.

The success of UPMC’s clinical pathway program is attributed to several operational and philosophical aspects.

In 2006, a software application was developed to provide real-time decision support via a user-friendly Web-based interface, referred to as the pathway portal. In effect, the software does the work of sorting through all the clinical algorithms for the physicians. The software also provides back-end information that serves as a valuable reporting source of user data, pathway adherence rates, and clinical trial accrual information.

Today, the pathway program is viewed as a software venture as much as it is a clinical content initiative. Lokay commented, “You can have all the best clinical content in the world, but if it sits on a shelf or a static website, you really don’t have anything to show for it, nor are you really driving that decision support.

“With the growing complexity of cancer diagnosis, workup, and treatment in the age of personalized medicine, pathways are a critical tool to helping the typical community-based oncologist stay abreast of the data,” explained absence of good data, the goal is to drive standardization. UPMC is home to the University of Pittsburgh Cancer Institute, a nationally acclaimed and recognized research center. So, it is not surprising that clinical trials are held in high regard and positioned prominently in the Via Oncology Pathways. The decision support tool displays open clinical trials upstream of relevant treatment recommendations. Trial accruals are counted on pathway. If a physician does not accrue to the trial, they are asked to provide the reason for that decision from a structured list. While much attention has been paid to the idea that UPMC, and now Via Oncology, adhere to a single treatment pathway model, this is often incorrectly interpreted to mean there is only 1 option or pathway for each disease. The reality is much more complex. The lung cancer pathways, for example, include 18 main branches with an additional 41 suboptions branching off of those. The committees stratify each disease by a number of attributes such as stage, histology, molecular pathology, and others. They derive 1 single best treatment for the general presentation of each unique intersection of those attributes. This process is executed with the rec- Ellis. In anticipation of these impending challenges, Via Oncology Pathways recently updated its extensive IT platform. The transformed platform will allow them to manage and update thousands of branches.

Transparency throughout the pathway development process is maintained by (1) opening disease committees to all physicians within practices using the pathways, (2) providing evidence reviews that detail the data and rationale behind pathway decisions, and (3) adhering to a clear conflict of interest policy. “We take conflict of interest very seriously and we have positioned ourselves so that we have no dependency whatsoever on the pharmaceutical industry that would cause a conflict of interest, whether perceived or real,” emphasized Lokay.

Thirty-three well-established disease committees—16 medical oncology committees and 17 radiation oncology committees&mdash; meet quarterly to review the pathways. Each committee is chaired by 2 physicians, 1 academic and 1 community- based. Separate medical oncology and radiation oncology committees operate for each disease, with 1 representative from each serving on the other’s committee. While Via has not yet developed surgical pathways, surgeons serve on committees for several diseases, especially those for which surgery is integral to care.

The inclusion of academic doctors in the Via Oncology Pathway decisionmaking process is somewhat of a distinguishing practice. It is a long-standing philosophy of UPMC’s pathway program that the process is best served by allowing the physicians who live by the pathways to design the pathways.

The disease committees strive to make evidence-based decisions whenever possible, but they do not adhere to a prescribed grading system. According to Brian Crandell, pathway pharmacist at Via Oncology Pathways, “We strive for the Phase III randomized trials, but unfortunately a lot of oncology drugs have been developed without a randomized trial against what is currently the standard of care.” In these situations, the committee may turn to meta- analyses for guidance, combine trial evidence, or make consensus-based recommendations.

Decisions are based first on outcomes. If there is no clear winner in terms of outcomes, toxicity is evaluated. Cost is considered when there is no clear winner in terms of efficacy and toxicity. There are not many cases where it comes down to cost. “Usually you get to a point where you go, wow, okay, this regimen is much more toxic than the other one,” said Lokay. In the ognition that the single best treatment may work for approximately 60 percent of patients. absence of good data, the goal is to drive standardization.

UPMC is home to the University of Pittsburgh Cancer Institute, a nationally acclaimed and recognized research center. So, it is not surprising that clinical trials are held in high regard and positioned prominently in the Via Oncology Pathways. The decision support tool displays open clinical trials upstream of relevant treatment recommendations. Trial accruals are counted on pathway. If a physician does not accrue to the trial, they are asked to provide the reason for that decision from a structured list.

While much attention has been paid to the idea that UPMC, and now Via Oncology, adhere to a single treatment pathway model, this is often incorrectly interpreted to mean there is only 1 option or pathway for each disease. The reality is much more complex. The lung cancer pathways, for example, include 18 main branches with an additional 41 suboptions branching off of those.

The committees stratify each disease by a number of attributes such as stage, histology, molecular pathology, and others. They derive 1 single best treatment for the general presentation of each unique intersection of those attributes. This process is executed with the recognition that the single best treatment may work for approximately 60 percent of patients.

Next, they consider whether there are other subgroups of patients for whom that therapy is not going to be a good fit, for example, patients who have poor performance status, can’t travel for weekly therapy, or have a contraindication to the primary treatment option. A subpathway is created for more commonly occurring profiles. Lokay clarified, “So, at the end of the day, for that node of the pathway, we may have 5 options, but 1 of those is considered the best for the more generalized population and the other 4 are suboptions for subpresentations. So, no, we don’t have just 1, but we do try to drive to 1 single best as a first choice.”

This approach allows solutions to be teased out when, from time to time, physicians call for more than 1 pathway option. Via believes that these requests are essentially the oncologists’ way of saying they have different kinds of patients that they see and they need more than 1 option. Crandell explained, “There is a logic process the committee goes through…and it is just a matter of us figuring out how to explain that in the software, through questions or getting the committee members to define more specifically when they would use each drug.”

In the 2011 calendar year, UPMC surpassed its on-pathway adherence goal of 80 percent. On-pathway decisions are considered to be: (1) treatment decisions made according to pathway recommendation and (2) appropriate decisions to take the patient off pathway, for example, upon reaching the last line of treatment.

When asked about the benefits of pathways, Ellis answered, “Our message to oncologists is straightforward. Payers are demanding a solution to the rising costs of cancer. While technology is the primary driver, not physician fees, the physicians are caught in the middle.” He went on to state, “It is imperative that physicians be the drivers of quality and cost containment for cancer, and if given the right tools for decision support and measurement, they can affect improvement far better than third-party intermediaries.”

A recently published study, led by UPMC Cancer Centers investigators and Via Oncology Pathways, reported that implementation and auditing of clinical pathways promoted uniformity of care across both academic and community care centers.

 In addition to reducing variability in care, pathways indirectly drive down cost by promoting the least toxic treatment options, according to Lokay. Detailing the benefits of UPMC pathways, Ellis mentioned the findings of 2 studies with Highmark Blue Cross Blue Shield, and 1 with IntrinsiQ, which demonstrate “a bending of the cost curve where the total cost of care for patients seen in pathways practices grows at a slower rate than the same costs for patients seen at non-pathways practices” (

More recently, UPMC/Via Oncology has partnered with Highmark Blue Cross and Blue Shield, the oldest and largest healthcare plan in New Jersey, to operate a pilot project that supports and evaluates Via Oncology Pathways in 2 oncology practices in New Jersey. Preliminary cost analyses for the 2 pilot practices indicate successful results in terms of total cost of lung and breast cancer care for the pathway practices relative to non-pathway practices. Results from the project with Horizon went on to state, “It is imperative that physicians be the drivers of quality and cost containment for cancer, and if given the right tools for decision support and measurement, they can affect improvement far better than third-party intermediaries.”

More recently, UPMC/Via Oncology has partnered with Highmark Blue Cross and Blue Shield, the oldest and largest healthcare plan in New Jersey, to operate a pilot project that supports and evaluates Via Oncology Pathways in 2 oncology practices in New Jersey. Preliminary cost analyses for the 2 pilot practices indicate successful results in terms of total cost of lung and breast cancer care for the pathway practices relative to non-pathway practices. Results from the project with Horizon BCBSNJ are expected to be published later this year.

Early on, pathway proponents envisioned a scenario where payers who were benefitting from pathway-generated savings in drug- and hospital-related expenses would be willing to proactively contract around and support pathways. The reality is that payers generally have not taken an interest in funding new initiatives. While this may have been disappointing to some, Lokay sees it as a good thing. “If the payers are calling the shots on which pathways to buy/hire, I don’t know how an oncology practice can cope in that world….I think we want practices picking the pathways they like and feel the most comfortable with.”

The natural evolution has been that pathways have become a way for oncologists to demonstrate, “This is the way we care for our patients, all of our patients.” Along those lines, practices are using pathways to forestall payers from introducing measures such as rate cuts, prior authorization, or specialty pharmacy.

Health reform vehicles such as medical homes and accountable care organizations are a big factor in why more practices have started looking at pathways programs. Practices are investing in and adopting pathways to better position themselves in their local market. To some extent, practices use pathways to demonstrate that their patients are receiving evidence-based and personalized care that takes into account things like toxicity and cost. “We have a number of practices that are jockeying to make sure that they either keep all their existing referral sources or maybe actually in the process grow their referral sources by attracting primary care medical home docs,” said Lokay.

What does the future hold for the pathway program at UPMC? Dr Ellis offered his insights: “We are already on track to achieve the vision of pathways that integrate seamlessly with the major electronic medical records and cover virtually all cancer types, phases of care, and modalities of care. We see the pathways being chosen by the practices, not the payers! We see the ability to measure outcomes that prove that standardization to the best evidencebased medicine improves patient outcomes and reduces costs.”

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; drafting of the manuscript; and critical revision of the manuscript for important intellectual content.1. Holcombe D. Clinical pathways programs: confusing choices for payers and physicians: part1: selecting the appropriate pathways program. JOMCC. 2010;3(5):10-11.

2. 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(suppl 3):52S-59S.

3. 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.

4. Beriwal S, Rajagopalan MS, Flickinger JC, Rakfal SM, Rodgers E, Heron DE. How effective are clinical pathways with and without online peer-review? an analysis of bone metastases pathway in a large, integrated national cancer institute-designated comprehensive cancer center network [published online ahead of print January 13, 2012]. Int J Radiat Oncol Biol Phys. doi:10.1016/ijrobp.2011.09.056.

Articles

Evidence-Based Oncology

UPMC Oncologists: Pioneers in the Clinical Pathways Movement

Forging a Pathway to Quality Cancer Care

Chronic myelogenous leukemia (CML) is an acquired disorder in which the Philadelphia chromosome, a translocation between chromosomes 9 and 22, is acquired in hematopoietic stem cells, resulting in expression of the Bcr-Abl oncoprotein. Over 5000 Americans are diagnosed with CML each year.

 Fortunately, the advent of tyrosine kinase inhibitor (TKI) therapy has dramatically extended life expectancy, with only 270 Americans expected to die of CML in 2011.

 The introduction of TKI inhibitor therapy has effectively transformed CML into a chronic disease, and this contributes substantially to the economic burden associated with CML—the median survival of these patients exceeds 20 years.

 A recent study demonstrated that medical costs for a patient with CML averaged $78,334 for just 1 year of treatment,

and TKI therapy must be given chronically or patients risk recurrence or progression to the advanced blast stage of CML, which can be life threatening.

The primary front-line therapeutic option for CML is individual TKI treatment, specifically with imatinib, dasatinib, or nilotinib. Imatinib was the first TKI to be approved by the US Food and Drug Administration and is used primarily as first-line therapy—it is not approved for use after patients have tried dasatinib or nilotinib.

 In contrast, both nilotinib and dasatinib were initially improved as second-line therapy after development of imatinib resistance.

 However, recent trials have demonstrated that these agents may have advantages over imatinib as first-line therapy, particularly in patients with intermediate- or high-risk disease.

 Longer-term follow-up of these studies is necessary to determine if these “second-generation” TKIs should become standard first-line therapy. For now, they are approved for newly diagnosed and imatinib-resistant disease only.

Patients achieving a complete cytogenetic response with a first-line TKI remain on that therapy as long as their disease is in chronic phase. If patients do not achieve a complete cytogenetic response after 12 months of treatment with imatinib, they may receive higherdose imatinib or switch to either nilotinib or dasatinib. For those receiving first-line nilotinib or dasatinib, treatment is often switched to the other second- generation TKI if their disease does not respond to initial therapy.

Some patients undergo mutational analysis of the Bcr-Abl kinase domain in order to choose the optimal second-line therapy, as both nilotinib and dasatinib are highly sensitive to specific mutations. In addition, mutational analysis can reveal the T315I mutation, which is resistant to all 3 TKIs; in patients with this mutation, allogeneic stem-cell transplantation is a reasonable option. Transplantation, which is the only curative treatment for CML, has lost favor as a first-line therapy with the advent of TKIs because of its high toxicity, including a 20% to 30% mortality rate,

 its limited feasibility (due to donor availability), and high cost.

If a patient receiving front-line TKI therapy achieves an insufficient response to treatment (less than complete hematologic response at 3 months, no cytogenetic response at 6 months, minor or no cytogenetic response at 12 months, or a partial cytogenetic response at 18 months) or if the disease reaches accelerated phase, treatment may be switched to a different TKI or an allogeneic transplant may be considered. Once a patient reaches blast crisis, options are generally restricted to a clinical trial or an allogeneic transplant preceded by a TKI with or without concurrent chemotherapy.

The management of CML is costly partially because patients continuously receive TKI therapy for many years. No clinical studies have yet shown that TKI therapy can be discontinued without patients experiencing relapse.

According to Medi-Span data as of December 2011, the wholesale acquisition cost per month of standard imatinib therapy is $5819, compared with $7882 for dasatinib and $8181 for nilotinib. The patent for imatinib expires in approximately 5 years, and a generic version could have a significant effect on pricing.

However, because some evidence suggests that nilotinib and dasatinib may have superior efficacy compared with imatinib in the front-line setting, these agents may be cost-effective in spite of their higher prices (in the present comparison). Further studies are needed to establish the cost-effectiveness of these second-generation agents relative to imatinib. Only retrospective health economic studies have examined the relative cost-effectiveness of nilotinib and dasatinib. For instance, a recent examination of claims from 521 patients with CML receiving second-line TKI therapy (452 receiving dasatinib, 69 receiving nilotinib) showed that patients taking dasatinib had nearly twice as many inpatient admissions (incidence rate ratio, 1.99; 

 = .047) and more than twice as many inpatient days (incidence rate ratio, 2.44; 

 <.001) compared with patients receiving nilotinib.3 In addition, patients given dasatinib therapy had $8288 more medical service costs (

 <.001), which were primarily associated with inpatient care. Finally, those taking dasatinib were found to be 13% less adherent to their medication than patients taking nilotinib (P = .009), despite the fact that nilotinib is taken twice daily and dasatinib is taken only once daily. Caution must be used when interpreting retrospective studies, but these data are intriguing. They are also consistent with another study of 267 patients, which demonstrated that patients with lower adherence to TKI therapy (in this case, imatinib) incurred higher annual medical costs.

 In this study, patients with a medication possession ratio (MPR) of 75% incurred an additional $4072 in medical costs in 1 year compared with patients having an MPR of just 10% higher, or 85%.

An interesting issue involving these TKIs is that they are oral drugs rather than injectable oncology agents, and are covered sometimes as part of the medical benefit versus the pharmacy benefit. In fact, since they are given on a continuing basis, many payers utilizing the pharmacy benefit elect to purchase and supply these agents through specialty pharmacy providers, who may have greater leverage with manufacturers (which results in somewhat lower prices).

Additional Drivers of the Cost of Care and Value

As expected, drug costs for patients with CML is the main driver of the cost of care, accounting for 42% of the total cost in one study examining costs incurred in the first year of care.

 This is true not only because TKIs are expensive drugs, but also because they are given indefinitely, until patients reach advanced phase disease, which may take many years. For example, 55% of patients receiving imatinib as part of the pivotal IRIS trial were still taking the drug after 8 years.

Aside from drug costs, both outpatient costs and inpatient costs are substantial as well, accounting for 27% and 26% of the total cost, respectively (

 Examples of outpatient costs include both disease monitoring and mutational analysis. Although patients may receive TKI therapy and remain clinically stable for years, their response to therapy requires frequent monitoring. The National Comprehensive Cancer Network recommends that patients achieving a complete cytogenetic response to TKI therapy should receive Bcr-Abl transcript monitoring every 3 months for 3 years and every 3 to 6 months thereafter. The cost of this monitoring ranges from $375 to $1500 for each test.

However, since this type of monitoring is necessary to determine when therapy should be switched, this represents a necessary cost. Mutational analysis, which is often performed before choosing a specific TKI, is over $500.

 Although this test is not absolutely necessary, it represents a good value for 2 reasons. First, it can provide a rationale for using imatinib over the more expensive second-generation TKIs if none of the mutations that are highly sensitive to either nilotinib or dasatinib are found. Second, if the patient is found to have the T315I mutation, no TKI therapy should be used, since that mutation is associated with poor response to all current TKI therapeutic agents.

 In the majority of patients, chronic myelogenous leukemia (CML) is highly treatable with today’s therapeutic agents. What has been the value of targeted treatment on value for the payer and the patient with CML?

The introductions of the targeted tyrosine kinase inhibitors, such as imatinib, have made a great difference in terms of outcomes to patients with CML. As a health plan, we support the appropriate use of targeted treatment with biomarker testing.

Considering the state of the art in CML treatment today, what are your objectives in setting medical benefit policy to ensure optimal treatment?

 We use prior authorization to ensure that biomarker testing has been done, according to the prescribing information, before targeted treatment is undertaken.

 What would you characterize as the determinants of good value in treating patients with CML today?

 We feel that the best value should be attained if we can achieve a remission with the fewest side effects. We would also prefer therapies with easy, convenient dosing to enhance compliance, especially since compliance seems to be a strong factor in averting recurrence. We also believe we can achieve greatest value if the regimen results in minimal interactions with other drugs the patient may be taking.

 What are the key objectives as a payer when managing patients with CML?

Obtaining a cure or remission with the fewest side effects would be the first objective. We want to avoid blast crisis, but it is difficult to determine who may be at higher risk for progression to blast crisis. It would be nice to have a biomarker to help in this respect. Stem-cell transplant is the most expensive treatment for CML. If we can avoid (not simply delay) the need for stem-cell transplant, that would create a very beneficial cost offset.

Does your plan contract with any major cancer treatment networks?

Although we don’t contract with major cancer networks, we do have preferred contracts with centers of excellence. The major benefits of these contracts are quality assurance and documentation of best outcomes. Most cancer networks want exclusive contracts, which would limit network negotiations with other needed providers geographically as a national health plan.

Does your health plan collaborate with any organizations to encourage members to participate in clinical trials in cancer treatment?

No, we don’t collaborate directly. Participation is determined by their employer’s choice of benefit plan (if such participation is covered). This can vary by the level of trial (phase I, II, or III) and what exactly would be covered (everything related to usual care minus the experimental drugs and costs associated with monitoring/usage/administration of such drugs). State regulations also influence this issue, as a number now require coverage for clinical trials for fully insured members (this does not apply to self-insured plans—which is why so many employers choose this approach, to avoid onerous, costly state mandates).

What types of investigational interventions hold the most promise for the future prevention/treatment of CML?

That’s a bit difficult to say, because CML is highly treatable in the chronic phase with today’s therapeutic agents. I do think targeted, oral drug combinations with companion biomarker tests offer the best direction, with the best tolerance regarding side effects.

Dr Kogan is based in Dallas, Texas, and is the medical director for a national commercial health plan.

Hoyle M, Rogers G, Moxham T, Liu Z, Stein K. Cost-effectiveness of dasatinib and nilotinib for imatinib-resistant or -intolerant chronic phase chronic myeloid leukemia. Value Health. 2011;14:1057-1067.

A UK National Health Service perspective on the cost-effectiveness of dasatinib and nilotinib compared with high-dose imatinib for patients with chronic-phase CML who are resistant to normal-dose imatinib and compared with interferon-α for people intolerant of imatinib.

Ghatnekar O, Hjalte F, Taylor M. Cost-effectiveness of dasatinib versus high-dose imatinib in patients with chronic myeloid leukemia (CML), resistant to standard dose imatinib—a Swedish model application. Acta Oncol. 2010;49:851-858.

Swedish researchers assess the cost-effectiveness of dasatinib versus high-dose imatinib treatment in chronic phase CML patients who are resistant to lower doses of imatinib.

Reed SD, Anstrom KJ, Li Y, Schulman KA. Updated estimates of survival and cost effectiveness for imatinib versus interferon-alpha plus low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukaemia. Pharmacoeconomics. 2008;26:435-446.

Researchers from Duke University evaluated survival data from the IRIS (International Randomized study of Interferon vs STI571) trial to update cost-effectiveness estimates, based on 19 months of follow-up, of imatinib versus interferon-α plus low-dose cytarabine in patients with chronic-phase chronic myeloid leukemia. When applying medication costs, incremental cost-effectiveness ratios were between $42,000 and $57,500 per quality-adjusted life-year.

Chronic Myelogenous Leukemia

Much has been said and written about the circumstances surrounding the launch of Dendreon’s innovation in cancer treatment, Provenge, a novel immunotherapeutic treatment for end-stage prostate cancer. In the months following the initial launch, capacity limitations were said to have constricted the potential uptake of the treatment in the medical community, masking the balance between sales and projected sales. As time went on and capacity issues were resolved, a Q code was assigned in July 2011 to the treatment, which improved billing issues, and expectations remained high among investors for product uptake. Those hopes were challenged as Dendreon

announced a slowing of sales versus estimates for the later quarters of 2011. This article will explore some of the issues behind the launch of Provenge, and discuss, from a community oncology perspective, whether the Provenge story reflects a rapidly changing landscape that moved faster than was anticipated for a new drug launch or rather serves as a claxon warning for revision of expectations for new drugs related to oncology for the future.

Typical Launch Delays in Production and Approval. 

Provenge, an autologous cell therapy, first won US Food and Drug Administration (FDA) approval in April 2010, and was officially launched the following month. CMS resolved national uncertainty over whether it would reimburse for Provenge at the end of March 2011, and after much national attention was drawn by the cost of the treatment ($93,000 for 3 infusions of the vaccine over 30-40 days), CMS announced that it would reimburse for Provenge when used for its approved indication. Private insurers continued to watch both the efficacy and the cost of the new treatment, and put into place a combination of prior authorization and post-claim medical reviews for physicians wishing to prescribe the treatment for their patients.

Capacity issues constrained the initial drug launch for much of the first 12 months it was on the market. Full-scale production wasn’t achieved until May 2011, which limited the number of sites at which the drug could be launched. Initial focus of distribution of Provenge was limited mostly to about 50 academic hospitals and cancer centers, despite more than two-thirds of asymptomatic or minimally symptomatic metastatic, castration-resistant prostate cancer (CRPC) patients being treated in community practice settings.

After the production issues were resolved, Dendreon Extended its sales force activities out into the community, targeting both oncology and urology practices. Those sites now number over 800, yet the investment community is still wondering if final 2012 sales will reach expectations.

Atypical Questioning of Launch and Sales.

 More questions have surrounded the launch of Provenge than any other oncology product in recent history. This launch is unique for a few reasons. It is a novel treatment, using the patient’s own cells to create the product. There is not likely to be a generic version of this treatment on the horizon. The patients do not have many other options—this is for a specific group of end-stage prostate cancer patients. Ultimately, survival is not an end product of this treatment, but it does seek to extend life for patients by a margin without complications of chemotherapy alternatives. Potential patients are found primarily in the community practices of both urologists and oncologists.

Questions from market analysts regarding the Provenge launch have centered around issues such as price, potential lack of patient demand, potential lack of education of physicians regarding access and administration, and particularly the probability and speed of reimbursement. None of these are new issues, and particularly not for oncology drugs. What happened during this product launch to cause such angst for Provenge?

Timing Is Everything: Provenge Entered the Market During Tumultuous Times

 Since 2003, when the Medicare Prescription Drug, Improvement, and Modernization Act (MMA) was passed, drug reimbursements for oncology have steadily declined. Medicare now pays based upon a market calculation of cost that doesn’t match the direct and indirect expenses that physicians incur to buy drugs for treatment. This Average Sales Price (ASP)-based reimbursement rate was adopted by Medicare in 2005 and more slowly by private insurers. By 2010, a cancer center (private or hospital-based) could see from 50% to 75% or more of its drugs reimbursed on an ASP basis. After factoring in both direct and indirect costs of drug acquisition, stocking, and handling, many practices could hope, at best, for breakeven on most of the drugs they stock. However, at the same time, private payers were rapidly ramping up oncology drug management processes, such as prior authorizations and reviews of medical necessity.

Increasing Pressures for Costly Technology. 

Medical providers, both hospitals and physician practices, have faced rapidly escalating demands for information technology, including electronic medical records that can track and report on certain measures. The American Recovery and Reinvestment Act of 2009 (ARRA) was signed into law on February 17, 2009. The ARRA was intended to kick-start healthcare investments in information technology, and in so doing, it created significant financial pressures on healthcare providers, which had already tight operating margins to fund technology initiatives.

Increased Patient Financial Responsibility.

 Following the passage of the MMA in 2003, new Medicare Advantage Plans and private insurers started pushing

greater financial responsibility for care upon the patients. Rising costs of care, driven by combination drug regimens and higher drug prices, even affected Medicare patients with regular Medicare insurance. If those regular Medicare patients did not also have supplemental insurance to assist with the 20% for which they are responsible, treatments could become unmanageable for those patients.

As operational margins tightened for medical practices, cash flow assumed great importance. Practices could often see delays in payment due to medical reviews and other payer processes of 30, 60, or even 90 days. In earlier years, margins on practice operations could more easily cover those cash flow delays, but by 2010, practices were feeling such financial pressure that timing of cash flow and cash outlays became very important, even if a drug were to be ultimately covered and funded. According to an Updated Practice Closings Report released by the Community Oncology Alliance in March 2011, more than 1000 cancer clinics nationwide have experienced closings or financial struggles to pay bills, have sent patients elsewhere for treatment, or have been acquired by other entities. Dr David Eagle, president of the Community Oncology Alliance, reports that these closings are due to both Medicare reimbursement cuts since 2004 and increasing numbers of private insurers following the Medicare pattern of reimbursement cuts.

With increasing health plan focus on appropriate use and prior authorizations came a large stick: If a treatment did not get appropriate prior authorization, or was found under subsequent medical review not to be covered, it was the practice that tended to absorb the loss.

It would not be uncommon by 2010 and 2011 for a practice or physician to look at a newly approved drug, try it initially for 1 patient, and observe not only the financial approval and reimbursement patterns for that drug, but also compare the results of the drug for their own patient against the published trial results. New drugs were being exposed to a much higher level of scrutiny in the real world medical community than ever before. No longer was simple approval by the FDA a blanket pass into uptake in the medical community.

Current Physician Community Perspectives on Provenge

For this article, local practices in Connecticut were interviewed on their current experiences and concerns regarding Provenge. While concerns about whether or not the treatment will be covered seem to have lessened, cash flow for payment, financial impact on the patient for copays and co-insurance (even for Medicare patients), and performance efficacy of the treatment in light of the cost of treatment continue to be significant themes.

 One oncology physician noted that they continue to see occasional problems with Provenge, primarily because of detailed oversight and insurance expectation that treatment will follow FDA approval very closely. Another practice administrator indicated that although they are one of the busiest practices in the area, they have not yet put any patients on Provenge, stating however that they believe one patient will soon meet the criteria. Conversely, it was noted that so much goes into pre-authorization before the patient is put into the process that the practice feels well assured of payment before the process begins.

It appears from the responding practices that cash flow is still a concern, but the depth of the concern may vary depending on the practice and the respondent. One practice administrator noted that drug distributor delays of drug payment due date of up to 90 days is very helpful. However, she went on to note that if a practice has more than 1 patient on Provenge, it needs to plan carefully for making that payment when the 90 days is up. If the practice has more than 1 patient on at a time, a due bill of over $100,000 could be significant for any practice. That administrator also wondered whether the payment terms for product could be restricted now that the Q code has been issued. Another physician noted that patient acceptance has been generally poor (from a financial rather than clinical standpoint). Another practice administrator noted that with practices across the country experiencing significant cash flow problems related to the Medicare implementation of new software (5010), any high dollar amount item for any reason is being closely scrutinized.

Concern was still expressed over the financial impact on the patient. Dendreon was complimented for the resources that it does make available to patients, but there were concerns over not only the impact on the patients who do not qualify for needed assistance, but also the burden on the patients and practice of the process for obtaining assistance. Even if assistance is found, the burden on human capital in the administrative and education process is significant, and may be untenable for a private practice or for the patient relative to the medical opportunity afforded by the treatment. A 2010 survey by the Association of Oncology Social Work reported that as many as 68% of cancer patients and caregivers reported that the patient is experiencing financial hardship due to medical bills. The survey also reported that about 49% had stopped treatments, skipped medications, or missed doctor’s appointments due to the financial burden, and many more never start treatment at all because of the catastrophic costs of cancer care.

Value, like anything, is found in the eye of the beholder. Both patients and physicians still express concern over the balance between the efficacy and benefit of the treatment versus the cost of obtaining that treatment. Even when patients have insurance that pays the bulk of the expense, cost is still considered as part of their evaluation process. The physicians who were interviewed, while not a significant sample, were interesting in that they all expressed either their own or their patients’ concern with the clinical experience in comparison with the literature or when compared with alternatives.

Conclusion: Both a Symbol and Victim of the Times 

As will be done with many more oncology treatments to come, Dendreon pushed to develop an individualized treatment for a patient population with few other alternatives. Under other circumstances, this innovation would have been lauded more than questioned. But, because of the maelstrom of financial pressures hitting practices, patients, and health plans alike, what was probably planned to be a conventional launch was beset with questions about value, pricing, efficacy, and slow uptake in its primary market, the community practice.

The new reality for any drug launch is now probably a litany of what Dendreon experienced:

• Increasing scrutiny of efficacy against alternatives (

; but probably with an expectation that such efficacy will be measured in half, threequarter, or full years rather than a few months).

• FDA approval may mean acceptance on Medicare formularies, but health plans may accept FDA approval or conduct their own reviews for what they consider to be medical appropriateness. Physicians may increasingly slowly adopt a product under FDA approval within their own practice, but observe treated patients for actual clinical experience in comparison with the published literature— as much for their own clinical satisfaction as for their ability to explain medical necessity to a health plan when prescribing the product.

• Patients may consider treatment options, even if FDA approved, and decide to proceed or not based upon their own financial benefit packageand personal situation. Dollars paid are being weighed heavily as debt incurred for a family that will linger once the patient is gone.

• Cost of product acquisition and timing of payment of that debt related to payment for treatment using that product are increasingly important to physician practices. Cash flow will be measured, and the higher-priced products may be subject to volume limitations on numbers of patients being treated at the same time to reduce exposure, and in the process, restrict market volume.

These concerns will remain whether treatment is delivered in a physician office or a hospital setting. Cash flow for oncology care and operational concerns have now become a permanent fixture in the treatment of cancer for the providers, the health plans, and the patients. Value is a function of all these pressures on the involved entities, as well as on the pharmaceutical company that develops the innovative treatment. For good or bad, that value equation has changed forever, and will actually continue to evolve as we learn more about the actual performance of all the alternatives for oncology treatment in the clinical setting. This may be a surprise message for financial market investors, but the physicians, patients, and health plans have been living with this reality for several years. Good products with strong efficacy will launch and do well, even if it is more slowly than expected based upon old market rules.

In the fall of 2011, while Provenge was still making news as a front-runner treatment for prostate cancer, another treatment, this time taken as a twice daily oral pill, was being approved for a slightly different indication.

 Zytiga, made by Johnson & Johnson, was first approved in 2011 for men with prostate cancer who had previously failed chemotherapy. However, a recent clinical trial was halted early by independent data monitors due to findings which, if approved, would move Zytiga into direct competition with Provenge for men with less advanced prostate cancer.

The nature of cancer research and treatment is that the unexpected is likely to prevail. With hundreds of clinical studies under development, new information is produced each year in peer-reviewed journals and clinical meetings, and submitted for approval. Placement of a new drug on the market requires a delicate balance of pricing strategy, proven efficacy under parameters whose importance sometimes varies with the beholder, and some degree of luck in terms of uptake on the part of patients, physicians, and health plans. If drugs are then held up in scrutiny to alternatives and found to have comparative issues on any of a number of fronts, it could be a challenge to its market success and position, no matter how new the drug itself is. There are differences in delivery, perceived convenience, and medical efficacy between Zytiga and Provenge that are now very much a part of the clinical discussion and ultimately will play out in the market.

1. Pierson R. Zytiga creeps up on Provenge prostate-cancer drug. Reuters.com website. http://www.reuters.com/article/2011/10/07/us-dendreon-zytigaidUSTRE7965JF20111007. Published October 27, 2011. Accessed April 27, 2012.

 .Published March 8, 2012. Accessed April 27, 2012.

2. Feuerstein A. J&J prostate cancer drug scores big win, hurts Dendreon, helps Medivation. Thestreet.com website. http://www.thestreet.com/_yahoo/story/11448569/1/jj-prostate-cancer-drugscores-big-win-hurts-dendreon-helps-medivation.html?cm_ven=YAHOO&cm_cat=FREE&cm_ite=NA

Is Provenge Angst a Symbol or Symptom of the Times?

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?

May

Forging a Pathway to Quality Cancer Care

Chronic Myelogenous Leukemia

Is Provenge Angst a Symbol or Symptom of the Times?

Testing for ALK-Positive NSCLC

Prostate Cancer

Value-Based Reimbursement in Oncology

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

Cancer Care Value-Learning From Others

On the Horizon for Multiple Myeloma

Oncology Hit Hard by SGR Debacle