This is the second article in a 3-part series discussing results from a recent survey of 418 patients with cancer.

Patient demographics and details on cancer types and treatment were published in the first article of this series.

This article discusses patients’ perceptions of the communication and counseling they received during cancer therapy.

It is important for healthcare professionals to communicate effectively with patients in a manner that ensures treatment efficacy, safety, and compliance. Professional organizations, such as the Commission on Cancer (CoC)

of the American College of Surgeons and the American Society of Clinical Oncologists (ASCO),

continue to call for proper treatment summaries and other forms of communication to be part of treatment plans. Effective communication and counseling should be considered an essential part of cancer treatment to ensure that patients adhere to, and are part of, the treatment plan.

Because cancer can impact patients of all ages, it is imperative for healthcare professionals to know from where patients are getting information and with whom they are sharing that information. Moreover, technology has increased the ways in which healthcare information is communicated. This article highlights patient communication preferences and describes how they have changed in recent years.

An essential part of cancer therapy is coordination of patient care. A variety of people were identified as the primary coordinator of care, including surgeons, oncologists, family members, nursing staff, family physicians, and patient navigators. Of those, patients most often identified surgeons and oncologists/ hematologists as the coordinator; patient navigators (eg, social workers, nurse case managers) were identified least often.

It should be noted that the patient navigator is a relatively new role. In 2012, however, the CoC added a new accreditation standard requiring cancer programs to phase in a process for patient navigation by 2015.

Therefore, patient navigators will likely increase in prominence over time. Also, patientcentered medical homes, specific to

oncology, are embracing the use of a patient navigator&#151;type position to facilitate care coordination and patient involvement.

One further interesting observation from the survey was that preferences were different based on sex and age (

). Men and older patients tended to rely on traditional healthcare providers like family physicians for information, whereas women and younger patients were more inclined to get information from patient navigators and oncology nurses.

Patients were asked which person on their care team provided treatment counseling, and their level of satisfaction. As shown in

, most patients gave moderate or high scores of satisfaction to the healthcare professional who provided treatment counseling. Surgeons and oncologists received the highest scores for satisfaction.

The list of topics covered during counseling was extensive. Almost all patients (95%) stated that they received information about follow-up care. Most patients also received counseling about pain management (65%), nutrition/exercise (62%), palliative care (51%), and chemotherapy plans (51%). Less than half of the respondents were provided counseling or information on life expectancy, support for family/caregivers, clinical trials, will planning, financial planning, or hospice care.

Given the CoC’s accreditation standard requiring cancer programs to phase in “a process to disseminate a comprehensive care summary and follow-up plan to patients with cancer who are completing cancer treatment,”

and the plethora of templates available for treatment planning, 4 patients were asked if they had received a treatment summary or transition plan. As shown in

, only half of respondents received such counseling. This was quite surprising, especially in patients who have completed treatment (ie, the cancer-free group).

Of the 197 patients who received a treatment summary or follow-up report, most obtained the report(s) from their surgeon (48%) or oncologist/hematologist (48%) (

). Surprisingly, only 18% of reports were communicated by the radiation oncologist, even though more respondents underwent radiation therapy (51%) than chemotherapy (41%). The American Medical Association’s (AMA’s) Physician Consortium for Performance Improvement developed 2 quality performance measures to document whether the treatment summary was communicated to the patient by the medical oncologist or radiation oncologist, respectively.

Written treatment summaries were well utilized. Most patients (96%) shared the report with other healthcare providers. Summary reports were commonlyshared with the patients’ family physician (77% of patients) or with other specialists (57%). Sharing the report with a family member was also common (61%), but the reports were rarely communicated to the patient navigator (5%) or pharmacist (5%).

The survey also asked patients how they obtained most of their health information. Most patients (83%) relied on their doctor/doctor’s office as their main source of healthcare information. The Internet was the second most common source of healthcare information, with 62% of respondents reporting its use. Common websites for information included WebMD (36%), the Mayo Clinic (13%), the American Cancer Society (12%), and the Leukemia & Lymphoma Society (4%). Survey respondents indicated that e-mail was the preferred method for communication of health information; this is in sharp contrast to 2 years ago, when postal mail was frequently selected (

Results from this survey indicate that surgeons and oncologists are the most likely healthcare professionals to provide counseling and treatment summaries to patients. While counseling was commonly practiced, the required treatment summary report at the end of therapy was only given to half of the patients who participated in this survey. It remains to be seen whether the advent of patient navigators improves patient communication and reporting. However, there appears to be room for improvement based on recommendations by the CoC and the AMA. The last article in this series will examine insurance and cost obstacles in cancer treatment.

To request an electronic copy of the 2012 Eisai Oncology Digest, please e-mail your request to:

.1. 2012 Eisai Oncology Digest. Woodcliff Lake, NJ: ReCon Marketing Solutions, LLC; 2012.

2. Trends in the 2012 Eisai Oncology Digest: patient demographics and cancer treatment goals. Am J Manag Care. 2012;4(3):136-138.

3. Commission on Cancer, American College of Surgeons. Cancer Program Standards 2012: Ensuring Patient-Centered Care. www.facs.org/cancer/coc/cocprogramstandards2012.pdf. Accessed April 18, 2012.

4. American Society of Clinical Oncology. Chemotherapy treatment plan and summary. www.asco.org/ASCOv2/Practice+%26+Guidelines/Quality+Care/Quality+Measurement+%26+Improvement/Chemotherapy+Treatment+Plan+and +Summary. Accessed April 18, 2012.

5. Butcher L. Medical home concept comes to oncology. Oncol Times. 2011;4(33):45-47.

6. PriorityHealth website. www.priorityhealth.com/about-us/press-room/releases/2011/oncology-medical-home.aspx. Accessed April 18, 2012.

7. Oncology Physician Performance Measurement Set. American Medical Association website. www.ama-assn.org/ama1/pub/upload/mm/pcpi/oncology-worksheets.pdf. Accessed April 18, 2012.

8. Eisai Oncology and Senior Health Digest. Woodcliff Lake, NJ: Cooper Research; 2010.

Trends in the 2012 Eisai Oncology Digest: Counseling and Communication of Cancer Treatment

Articles

Evidence-Based Oncology

In 2011, one large pharmacy benefit manager spent more than $25 per member per year (PMPY) on oncology specialty pharmacy, an increase of $4 PMPY from 2010 (Table). Spending is forecasted to exceed $40 PMPY by 2014 (Figure 1). Emerging oral cancer drugs are shifting costs from medical benefits to pharmacy benefits. With increasing numbers of expensive specialty pharmacy oncology drugs on the market&#151;and hundreds more in the pipeline—it is clear that improvements in oncology pharmacy management are needed.

At the 2012 Academy of Managed Care Pharmacy Annual Meeting, a panel made up of a patient advocate, a cancer survivorship specialist, health plan representatives, an oncologist, and a health services researcher discussed the desired outcomes of oral oncology drug management, practical next steps, and gaps in and barriers to implementation.

Over the last 10 to 20 years, the introduction of new therapeutic agents has markedly improved overall survival for many types of cancer. In most cases, however, supporting data have not kept up with these advances, leaving knowledge gaps that make coverage and treatment decisions difficult. For many patients, cancer has become a chronic condition requiring long-term therapy. These evolving trends are bringing long-term cost implications. Payers and health plans find themselves attempting to manage practice patterns, provider and patient behavior, treatment options, and quality&#151;a huge administrative cost burden. For many patients,cancer has become a chronic condition requiring long-term therapy. These evolving trends are bringing long-term cost implications. Payers and health plans find themselves attempting to manage practice patterns, provider and patient behavior, treatment options, and quality—a huge administrative cost burden.

John Cruickshank, DO, MBA, chief medical officer, Lovelace Health Plan, provided an overview of outcome indicators and treatment pathways during the program. “Payers are beginning to expect that improved outcomes by an agent or regimen be demonstrated prior to full reimbursement,” he explained. “Historically, the overall survival end point has been the gold standard for oncology drug approval by the FDA, but that is changing rapidly.” Recently, approvals have been granted based on surrogate end points, such as objective response rate, progressionfree survival, disease-free survival, and time to progression. A major problem with surrogate end points is that they often do not translate into long-term survival benefit. The use of different end points across trials makes comparative analyses difficult.

The panelists and attendees agreed that standardized treatment pathways that take into account comparative effectiveness and cost data are the ideal foundation for coverage decisions. The consensus among the panel was that preferred pathways will help relax prior authorization requirements and other barriers to approval, thereby lowering cost for managed care organizations while easing access for both patients and providers. Health plans would like to be able to use treatment guidelines or pathway programs for a balance of clinical, qualitative, and economic features to yield the most cost-effective treatment results. Numerous treatment options, a poor evidence base upon which to make decisions, and wide variability in treatment plans present barriers to making this a reality, however.

Existing guidelines do not offer a single drug recommendation in most cases, do not include cost information, and are not always in agreement with one another or with compendia. To achieve desired outcomes, the numbering the program. “Payers are beginning to expect that improved outcomes by an agent or regimen be demonstrated prior to full reimbursement,” he explained. “Historically, the overall survival end point has been the gold standard for oncology drug approval by the FDA, but that is changing rapidly.” Recently, approvals have been granted based on surrogate end points, such as objective response rate, progressionfree survival, disease-free survival, and time to progression. A major problem with surrogate end points is that they often do not translate into long-term survival benefit. The use of different end points across trials makes comparative analyses difficult. of pathways in use must be reduced to a manageable number. Until these challenges are overcome, panelists and attendees both agreed that National Comprehensive Cancer Network (NCCN) guidelines are an excellent resource and that their consistent use as a basis for decision making will reduce barriers to access for appropriate therapies. The panelists summarized other specific suggestions that came out of session workshops (

Applying Oncology Formulary and Benefit Design Innovations

The panel discussed innovations in formulary and benefit design models through which to better manage oral oncology drugs. With the introduction of more effective and expensive oncology drugs, vigorous debates have ensued about the overall value of treatments, said Jeffrey Dunn, PharmD, MBA, formulary and contract manger,

). Payers are actively applying payment reforms and quality measurement to cancer services.

Health information technology (HIT) is a powerful tool that should be better exploited by pharmacy management. Effective application of HIT can enable rapid identification and incorporation of emerging data and provide a common data platform that supports decision making and patient monitoring.

HIT might also be used to address fragmentation of care between specialty pharmacy and the oncology care team. Fragmentation poses a significant management barrier. For example, logistic procedures may differ from drug to drug or between classes of drugs on both the payer and provider sides of healthcare. This issue is particularly relevant to oncology because the medication regimens of cancer patients frequently evolve.

Dunn emphasized that improved communication and collaboration between plans and oncologists will be vital to success and that achieving desired outcomes will be impossible without them. Successful management of cancer care requires a strategy that supports rather than hinders successful payer/physician collaboration.

The panel supported patients and patient support groups as important stakeholders whose perspectives should be considered during overall benefit design&#151; especially with respect to issues such as copay versus coinsurance, emotional distress, supportive care, advance planning, and the impacts on decision making of dynamics between plans, employer, oncologist, and family/caregivers.

In summary, the panel agreed that a tiered oncology benefit model will undoubtedly be a part of designs going forward. Overcoming barriers will be helped by integration of specialty pharmacy and investing in technology that improves access to data and collaboration. Other valuable approaches discussed included utilization of case management programs and certain aspects of patient-centered medical homes, value-based models, and adaptation of education and diseasemanagement strategies that have been proved effective in other disease states. Furthermore, ownership of outcomes should be shared among key stakeholders, including patients, payers, and healthcare providers.

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.

Achieving Quality and Containing Cost Through Oncology Pharmacy Management

Pertuzumab, a new HER2-positive breast cancer drug, is being launched at a 31% premium to the price of trastuzumab. This is an aggressive strategy that will substantially increase the cost of treating patients with metastatic HER2-positive breast cancer, while also aiming to deliver the best outcomes for patients.

Pertuzumab will be used as an add-on to trastuzumab to treat patients. Progression- free survival was boosted by 6.1 months when the drugs were used in combination in the CLEOPATRA study.

With payers already anxious about the rising costs in oncology, an 18-month course of the combination treatment is estimated to reach more than $180,000. This cost sets the bar high for the future, as expensive targeted drugs are expected to be used increasingly in combination to deliver the best outcomes.

To examine these treatment benefits, cost concerns, and potential insurance coverage strategies, AJMC’s co-editor-in-chief, Michael E. Chernew, PhD, professor, department of healthcare policy, Harvard Medical School, moderated a panel discussion with Lee Newcomer, MD, MHA, senior vice president, oncology, UnitedHealthcare, and Sandra M. Swain, MD, medical director, Washington Cancer Institute, Medstar Washington Hospital Center.

Dr Swain, I am interested in the current treatment landscape for patients with breast cancer. If you have any thoughts on how physicians choose breast cancer treatments for their patients, it would be interesting to hear them.

There are a lot of different treatment paradigms for breast cancer and it really depends on if you are talking about early stage disease or metastatic disease. Let’s start with metastatic disease. Unfortunately, even with some of our very effective treatments, we really don’t affect survival in a lot of cases of metastatic breast cancer. However, breast cancer has really been categorized now into different kinds of breast cancer&#151;ER-positive breast cancer, triple negative breast cancer [meaning there is no estrogen receptor or HER2], and HER2-positive breast cancer [in which patients have the HER2 oncogene that is overexpressed]. So, it’s very complex; you can’t just answer that with 1 answer. The way an oncologist would choose is to look at the biology of the tumor [to see] if it has the receptors or not. For example, if the tumor had the HER receptor with metastatic disease and it was first line you would choose trastuzumab. And, with the recent data in the CLEOPATRA study showing that the addition of pertuzumab to trastuzumab plus docetaxel actually has a large benefit, oncologists would consider this also at this point.

Dr Chernew: So, can you provide a brief overview of the CLEOPATRA trial?

The CLEOPATRA trial was a prospective, phase 3, randomized study in patients who had not received any chemotherapy for metastatic HER2-positive breast cancer. The study included 808 patients and they were randomized to either receive placebo plus trastuzumab plus docetaxel [control group] or pertuzumab plus trastuzumab plus docetaxel [pertuzumab group]. It was first-line treatment, and the end point of the study was to look at an independently assessed progression-free survival. It really had a spectacular result in my opinion. It was a progressionfree survival advantage of 6 months. This was actually a placebo-controlled study, so even though progression-free survival can be a difficult end point, it was clear in this study that there really was a benefit to the addition of the drug pertuzumab. The interim analysis of survival showed a trend in favor of pertuzumab in the initial report that we released at the San Antonio Breast Cancer Symposium and published in the New England Journal of Medicine in December 2011, but most recently we’ve reanalyzed the survival and, actually, a press release came out this past June showing that there was a survival benefit also with the addition of pertuzumab. This top-line data was submitted to a major meeting, so hopefully it will be presented in the next few months.

As a first-line treatment, how many breast cancer patients would be eligible? Just the patients who would have the correct target&#151;the HER2 target?

The patients with HER2-positive overexpression are approximately 15% to 20% of breast cancer. And, the indication is only for patients who have not had previous chemotherapy. It wouldn’t be for someone who’s had trastuzumab or other drugs or second-, third-, or fourth-line treatments. It’s only for first-line treatment.

Dr Chernew: OK, and that would be approximately 15% or less because of the exclusions?

Maybe a little less than [the general population of patients with breast cancer]. Per year, it would be 15%, but of the patients now, it’s certainly going

to be less because a lot of patients now would have had other treatments.

The manufacturers are estimating that there would be approximately 8000 women who would have HER2-positive metastatic breast cancer, per year, in the country. That’s a fair estimate.

Dr Chernew: One of the biggest challenges&#151; because it sounds, clinically, like there are a lot of optimistic results— is how we might finance access to this treatment. The cost of the pertuzumab and trastuzumab combination is approximately $187,000 for a course of treatment over the entire duration. So, Dr Newcomer, how do you think plans might respond, how do you think oncologists might respond, and what general strategies will be utilized to provide access to this drug?

Well, I am in complete agreement with Dr Swain in that pertuzumab is a good drug. The trial showed a clear benefit and the benefit was probably one of the larger ones we’ve seen in a long time. Therefore, I would be quite surprised if there wasn’t ready access to pertuzumab from any payer for the indication for which it’s approved. So, as first-line therapy in combination with trastuzumab and docetaxel, I can’t imagine that anyone wouldn’t cover that. That said, it’s expensive, there’s no question. From a total expense though, it’s a very small population compared with all of the women with breast cancer. And, the way that we deal with that, as does every payer in the country, is we simply build it into the premium, and the premium for the next quarter goes up. So, there isn’t a way to pay for this other than simply passing the costs on in the premium, which means everyone who buys health insurance will see a slight increase.

Dr Chernew: Do you do modeling&#151;because the population is so small—to show how big that increase might be? Is the premium increase small because of the small number of women, despite the per treatment sticker price?

Yes, we actually do model all new technologies. We generally model them approximately 6 to 12 months prior to their emergence into the market and start building that into the premium in anticipation of the new technology coming on board. I don’t know the exact amount for pertuzumab and wouldn’t be able to release it anyway, but that is a process that we do routinely, looking for the new drugs coming out or other new technologies, estimating their costs and how many people would be using it, and building that into the premium.

Dr Chernew: In certain cases, and you were very clear in your earlier answer, there’s utilization of drugs or, more broadly, new technologies beyond the populations that were originally studied or for whom it was originally approved. Do you think that’s a big

issue in this particular case and, if so, how do you think your plan and other plans might deal with that issue?

I think it clearly is an issue to consider. Every drug that comes to the market eventually finds new uses as further clinical trials are undertaken and they may be reflected on the FDA label. What we’ve done at UnitedHealthcare is turned to the National Comprehensive Cancer Network (NCCN) recommendations to decide when there is enough evidence for coverage. If the NCCN recommends it in their guidelines, then we provide coverage. Other insurers are examining the evidence, whether using their own staff or other sources, but we are going to see people testing this drug in other indications. They may use it as an adjuvant with trastuzumab. They may try using it in second- and third-line treatments. If the evidence shows there is still a benefit, then I do think you will see a use expand.

Dr Chernew: Do you think there will be that type of experimentation prior to rigorous studies in those other populations?

There already are other people attempting to use it that way, and as I was discussing with Dr Swain prior to the call, almost 90% of our requests for this drug in the first week were for indications other than what the CLEOPATRA trial showed. And, we don’t cover in that circumstance until there is proper evidence.

Dr Chernew: When you say other indications than what the CLEOPATRA trial showed, do you mean indications that were studied and there wasn’t an effect or do you mean indications that simply weren’t studied in the CLEOPATRA trial?

In clinical situations that simply weren’t examined in the CLEOPATRA trial; for example, patients on their fourth or fifth line of therapy.

Dr Chernew: More broadly, what drives the cost of drugs in cancer care?

Well, I think what the companies say is that it’s very expensive to develop these drugs, such as the clinical trials. The CLEOPATRA study was 808 patients&#151;I don’t know how many millions of dollars it cost, but it cost a huge amount of money. Sometimes the number you see is a billion dollars to develop a drug. And, many of the drugs that they start developing don’t go to market, so then they don’t recoup any of those costs for developing those drugs. However, I think that the pricing is as high as the market can bear. And, so there’s really no link right now between the pricing and effectiveness of drugs. For example, many of these other drugs that are chemotherapy drugs used for second-, third-, fourth-line treatment in breast cancer don’t have survival benefit and are expensive, and yet that really isn’t taken into consideration. I think we need to do that, certainly in the future. One of the things that I am very interested in doing is not getting incremental benefits with our drugs. I think what’s happened in the past is that a lot of drugs have been approved when it’s later-line treatment because there’s not a lot of treatment for the patient—the bar is lower. In other words, the benefit is not as great. In addition, the patient may have a lot of toxicity and may not have the benefit, so there’s a high cost there, too.

Dr Chernew: In this case, it seems pertuzumab provides a lot of value at a very high cost and, if I understand Dr Newcomer’s earlier answer, the benefit seems great in this case and the overall population seems relatively small. So, the overall premium impact isn’t enormous and he [Dr Newcomer] would expect that there would not be restrictions on access to pertuzumab. Is that generally your sense, Dr Newcomer?

The restrictions that will be placed will involve ensuring that the HER2 gene is actually overexpressed, so that the drug isn’t used on HER2 underexpressed patients. This was a problem when trastuzumab initially came out. I would expect the same thing here. But, within the same criteria that the trial used, I do think there will be readily available coverage.

Dr Chernew: I think that breakthroughs such as this lead to a lot of excitement. However, it does lead to a general dilemma about financing access to expensive, although I think in this case considered valuable, care.

First, I would love to hear Dr Swain’s opinion and others on whether the CLEOPATRA trial should have had a third arm. That arm would have compared the control regimen used until progression followed by the addition of pertuzumab until the second progression. The study would then compare overall survival between the groups. One way to reduce the total cost of therapy is to use the drugs sequentially rather than as an initial combination. This would reduce the time required to use the more expensive medication if the results were comparable. Yet manufacturers, for obvious reasons, don’t ever do that trial. If sequential therapy obtained the same type of responses, it would significantly reduce the amount of drug necessary to treat them.

Michael E. Chernew, PhD; Lee N. Newcomer, MD, MHA; and Sandra M. Swain, MD; examine the treatment benefits, cost concerns, and insurance coverage strategies for pertuzumab.

Treatment and Cost Implications of Pertuzumab

Beyond providing prognostic information, molecular biomarkers can help optimize therapy decisions. Predictive biomarkers are beginning to help physicians assign value to associated therapies in terms of likelihood of benefit and benefit-to-risk profiles for individual patients. A predictive factor is a baseline patient or tumor characteristic that identifies a specific qualitative outcome (eg, response or survival) driven by a treatment.

Healthcare providers and payers hope to be able to use predictive biomarkers to rationally apportion therapy. “We want to enrich the treated population with those who are likely to benefit from therapy,” explained Mark Green, MD, chief medical officer, Xcenda, who led the roundtable discussion Prognostic vs Predictive Biomarkers and the Role of Companion Diagnostic Testing in Payer Decision Making during the 2012 Academy of Managed Care Pharmacy Annual Meeting. “Individuals likely to benefit should be willing to accept the risks of receiving that therapy, namely: costs for that particular treatment, loss of opportunity to try something else at that point in time, and treatment-related toxicities.”

On the other hand, he said, “Individuals whose tumors fail to express a biomarker directly predictive of a reasonable likelihood of response to a certain therapy would be much better served by exploring other therapies and not exposing themselves to an extremely low likelihood of benefit with no reduction in risk.” The loss of opportunity for trying an alternative therapy that might offer a better chance for response is a significant risk to this group.

When a biomarker test is capable of predicting response to a particular therapy, payers should have the opportunity to incorporate that test into their drug benefit management strategy. It is Dr Green’s opinion that by encouraging and covering testing, payers can facilitate rational treatment and coverage decisions. He is expecting that electronic medical records will help bolster awareness, buy-in, and integration of biomarker testing.

According to Green, the field is still finding its way in actualizing the use of biomarkers, not only for therapy selection but for coverage decision making. “It is a new world for providers, payers, patients, and the entire consortium of healthcare stakeholders, but we have to make rational use of them,” he commented.

Applying biomarkers in this way, he cautions, will require discipline and biomarker assays of excellent quality that are associated with high reproducibility, specificity, sensitivity, and accuracy. It will also require stakeholders to agree upon test criteria, thresholds, and decisions related to companion diagnostics. Once that happens, according to Green, plans and providers should be in a position to address the optimum strategy for care. “It is evidence-based, it is science-driven, it is an opportunity cost for optimized patient care and it is a responsible behavior. That is what we are striving for and that is where we need to be going,” he remarked.

An exciting development in the field of predictive diagnostics is the US Food and Drug Administration (FDA) approval of crizotinib (Xalkori), along with a companion diagnostic test, for patients with ALK-positive locally advanced or metastatic non-small cell lung carcinoma (NSCLC). Although crizotinib costs more than $9000 per month, the response rates in patients with ALK-positive tumors are dramatic. The majority of eligible patients responded to therapy (

), demonstrating the robust enrichment in likelihood of response achievable with predictive biomarkers.

Giving these targeted agents a try in everyone is not an advantageous approach for a number of reasons. These drugs are extremely expensive and there is the issue previously raised about giving someone a therapy from which they are not likely to benefit while exposing them to all the associated costs. The overall rate of response to epidermal growth factor receptor (EGFR) inhibitors among patients with advanced NSCLC positive for an EGFR mutation is around 70%, while in patients without an EGFR mutation, it is essentially zero. Use of the EGFR inhibitor gefitinib as initial therapy for patients with EGFR-mutation-negative tumors suggests targeted therapy can actually worsen progression-free survival (

). In addition, some trials show that if you don’t test and instead simply randomly assign patients to either

erlotinib or chemotherapy as first-line therapy, overall survival may be significantly worse in those individuals who are assigned to receive targeted therapy rather than chemotherapy as first-line management. Dr Green elaborated, “So you have to have the test results if you want to use this targeted therapy in the first-line setting and if the patient carries a mutation and you use gefitinib or erlotinib first-line, the likelihood of response is extremely high.”

Dr Green reiterated the goal of predictive therapy as, “You want to be able to dichotomize a population into those who have a high likelihood of benefit and those who do not.” The key, he says, is to avoid missing that person who has a chance to receive a therapy that may provide a 70% to 80% chance of response and has been shown to remain active at 12 months or longer. “We are looking to be able to rationalize, not in the sense of justify, but in the sense of being able to think clearly of how to assign therapeutic recommendations.”

Rationalizing Treatment and Coverage Decisions With Predictive Biomarkers

Despite rising medical costs within the US healthcare system, quality and outcomes are not improving. Without significant policy reform, the cost-quality imbalance will reach unsustainable proportions in the foreseeable future. The rising cost of healthcare in part results from an expanding aging population with an increasing number of life-threatening diseases. This is further compounded by a growing arsenal of high-cost therapies. In no medical specialty is this more apparent than in the area of oncology. Numerous attempts to reduce costs have been attempted, often with limited benefit and brief duration. Because physicians directly or indirectly control or influence the majority of medical care costs, physician behavioral changes must occur to bend the healthcare cost curve in a sustainable fashion. Experts within academia, health policy, and business agree that a significant paradigm change in stakeholder collaboration will be necessary to accomplish behavioral change. Such a collaboration has been pioneered by Blue Cross Blue Shield of Michigan and Physician Resource Management, a highly specialized oncology healthcare consulting firm with developmental and ongoing technical, analytic, and consultative support from Cardinal Health Specialty Solutions, a division of Cardinal Health. We describe a successful statewide collaboration between payers and providers to create a cancer clinical care pathways program. We show that aligned stakeholder incentives can drive high levels of provider participation and compliance in the pathways that lead to physician behavioral changes. In addition, claims-based data can be collected, analyzed, and used to create and maintain such a program.

The overall incidence of cancer in the United States is projected to increase by 45% in the next 2 decades from 1.6 million in 2010 to 2.3 million in 2030. Direct medical costs associated with cancer are also projected to increase exponentially from $104 billion in 2006 to more than $173 billion in 2020 as a result of increases in both the cost and quantity of cancer therapies.

Newer cancer treatments are not only likely to be more expensive than the existing standard of care, but they will expand the pool of available treatment options.

Despite these rising medical costs and treatment options, quality and outcomes are not improving.

Without significant policy reform, the cost-quality imbalance will reach unsustainable proportions in the foreseeable future.

Many factors play into the rising costs of healthcare, including an aging population, an expanding arsenal of therapeutics for chronic disease states, increasing regulatory demands on stakeholders, inefficiencies in delivery, and archaic information technologies. All of these factors result in significant variations in practice patterns among medical oncologists.

Costs can vary dramatically because physicians often treat patients with the same condition differently in choice of drugs, referrals for surgery and radiation, referrals for palliative and end-of-life care, and types of supportive care. Strategies such as prior authorization and decreasing fee schedules have been implemented in an effort to lower healthcare costs.

However, because neither of these strategies addresses practice variances or the rapidly rising cost of cancer therapeutics, their impact on healthcare costs has been of limited benefit and brief duration.

Clinical pathways are a method to reduce unnecessary and costly treatment variation; however, physician participation is crucial for their success.

The perceived challenge of cookbook-style medicine to physician autonomy from an external authority, such as insurance companies or academic advisory boards, can be one barrier to pathway adoption among others such as time constraints and comfort with previous practice patterns.

Without accountability or incentives, physicians might comply partially with the terms of a pathway program or not participate at all. Therefore, a collaborative effort between pathway-developing parties and oncology groups is needed.

Physicians directly or indirectly control or influence the majority of cancer care costs.

Therefore, physician behavior change can be used as a surrogate marker of cost savings, which can be difficult to demonstrate as a result of evolving patterns of care, new drug technologies, patent expirations, and data capture problems from revenue code and charge bundling to name a few.

This article details a collaborative statewide cancer clinical pathway program in which provider network medical oncology physicians played an integral role in developing oncology clinical pathways. The success of the program was determined by evaluation of physician compliance with the pathways and their behavioral changes in the first year of the program resulting from the inherent difficulties in determining cost savings in this setting.

In mid-2009, 3 groups&#151;Blue Cross Blue Shield of Michigan (BCBSM; Detroit, Michigan), a large single-state not-forprofit BCBS plan; Physician Resource Management (PRM; Novi, Michigan), a state physician organization; and Cardinal Health Specialty Solutions (CHSS; Dublin, Ohio), an oncology benefit management company (previously P4 Healthcare)—partnered to develop a clinical pathway program whereby physicians would jointly develop the content, structure, and implementation of the program pathways. Involving physicians in the clinical pathways development process would provide an incentive for physicians to participate in the pathways themselves. Care pathways for breast, colon, and lung cancer were developed in the first year of the program and expanded by 5 additional malignancies in the second year. The program would benefit all parties involved in patient care, including patient, provider, and payer, by aiming to improve the consistency and quality of patient care while also reducing costs. The clinical cancer care pathways program was operated and funded through the Oncology Physicians Resources (OPR; West Bloomfield, Michigan) group, an existing statewide physician-owned general purchasing and management organization and subsidiary of the Michigan Society of Hematology and Oncology (MSHO; Rockingham Royal Oak, Michigan). PRM is an administrative arm of OPR and would manage the BCBSM pathway program.

Before the development of this partnership, BCBSM instituted a payfor- performance program in 2005 for Michigan physicians, the Physician Group Incentive Program (PGIP). This program added a physician organization fee component to each professional service payment. The physician organization component was held in an incentive pool and fully distributed twice each year to physicians who participated in PGIP. It was determined that the BCBSM cancer clinical care pathways program would be placed under the aegis of PGIP and that funding would be paid directly to OPR/PRM according to PGIP bylaws. Figure 1 presents a schematic of steps involved in the pathways development and the implementation of BCBSM oncology treatment pathways.

One of the first critical steps in the development of the BCBSM pathway program was to align stakeholder incentives so that all interests would be taken into account. BCBSM wanted to develop a program that would improve clinical outcomes with more predictable costs, thereby bending the cost curve downward for future oncology care. Oncologists wanted reimbursement stability. CHSS wanted to prove its value-added benefits to the process by not only receiving a fee for service for their technical support but also sharing in both the upside and possible downside of the program results attributable to pathway compliance. All 3 stakeholders agreed that, given the appropriate incentives, provider behavior could be modified in a self-governing process in which claims data would be used to monitor compliance.

PRM and BCBSM agreed on ways to reward physicians for using pathways. BCBSM provided each physician participant a $5000 payment for the first year of the pathways program to cover any extra costs involved and to provide a financial incentive to participate and meet approved compliance thresholds. In addition, the reimbursement rate for several generic therapies associated with the specific clinical pathways was increased to remove the perverse incentives created by average sales price&#151; based reimbursement (13 drugs were modified in 2010). Evaluation and management codes would also be increased (10%) for pathway program participants as a result of compliance in year 1. Payments were also made to PRM to serve as the coordinating center for this statewide effort from the BCBSM PGIP incentive pool. With those monies, PRM elected to make payments to physician groups for their participation, support the development of clinical pathways, provide software developed by CHSS, and subcontract with CHSS for additional services. BCBSM incentives and fee schedules were also reviewed to assess how payer incentives aligned with best practices.

PRM selected regional leaders to serve on a steering committee. The steering committee comprised 12 regional network oncologists from academic-based practices and large and small community- based practices. It was co-chaired by the CHSS chief medical officer and an OPR officer as nonvoting members. On the basis of published scientific and clinical evidence and national guidelines, the steering committee developed the most up-to-date and effective oncology care pathways for breast, lung, and colon cancer and supportive care using granulocyte colony-stimulating factors, erythropoietin stimulating agents, and antiemetics. Treatment, efficacy, toxicity, and cost (in that order of priority) were considered in all pathway regimen selections. National Cancer Institute&#151;designated clinical trials and/or decisions for palliative care were mutually agreed upon to be included in all pathways. The steering committee also embraced molecular diagnostics in breast, colon, and lung cancer as part of the pathways process.

The oncology pathways were introduced to the remaining oncologists within the broader BCBSM network for their review and input. All recommendations were evaluated by the steering committee. These steps were critical and ensured that the valuable experience and expertise of each network physician was considered before pathway adoption. The pathways are organized by line of therapy, and they include molecular profiling, histologic profiling, treatment indication, and stage. The steering committee continues to meet quarterly and on an ad hoc basis.

Before the pathway finalization, the criteria for selection and protocols underwent review by BCBSM; however, BCBSM did not play a role in protocol selection. It was determined from the beginning of this partnership that this statewide initiative would be best positioned for success if BCBSM kept its role to that of an objective third-party funder with a strong interest in the outcomes of the program but with no direct influence in the determination of what ultimately constituted the clinical pathways.

The BCBSM oncology care pathway program acknowledged that pathways are not a substitute for physician judgment and that some variance can and should be expected to allow for individual treatment on the basis of unique patient needs. Therefore, it was agreed that compliance thresholds for participating physicians should not be set at 100%. For cancer treatment in the adjuvant and metastatic setting for breast, colon, and lung cancer, a 70% compliance rate was set as the threshold for the first year and 80% for subsequent years with reporting on both as a means of communication with and education for the provider network. It was also agreed that an 80% rate of compliance would be appropriate for supportive care in the first and subsequent years. Most pathway deviations would be rendered noncompliant and part of the allowable 30% noncompliance rate. However, an appeals mechanism was put in place via portal. In rare instances, nonpathway approaches could be challenged proactively when standards of care are dynamic (eg, in triple-negative breast cancer). This could be addressed via an ad hoc steering committee meeting or a proactive appeal and would include oversight committee evaluation within 48 hours.

Compliance was measured through claims submitted to a proprietary claims cycle management software tool, eob- ONE (Cardinal Health; Dublin, Ohio). It was augmented and validated with data directly from the insurer for patients with breast, lung, and colon cancer who started new lines of antineoplastic therapy on or after January 2010. Additionally, physicians could submit information through a secure web portal or fax (eg, clinical trial schema and hospice care notifications). Collecting data in this manner created no additional work for the practices. Physicians were notified of their compliance scores through quarterly reports from CHSS and were\ allowed to reconcile noncompliant determinations by providing additional data through the appeal section of the CHSS web portal. Aggregated program compliance was presented to BCBSM at quarterly meetings and to participating physicians at semiannual conferences. OPR had the responsibility of notifying and counseling practices with compliance issues.

More than 80% of Michigan private practice medical oncologists participated in BCBSM’s PGIP in the first year. Prepathway physician practices closely followed pathway guidelines, and baseline pathway compliance was therefore high at 88% when using the 70% threshold. This rate increased steadily in the first year of the program to 95% (Figure 2). Clearest among physician behavioral changes was a reduction in treatment variation. Although pathway guidelines allowed approximately 120 different chemotherapy combinations for breast, colon, and lung cancers, the vast majority of patients were treated with 1 of 30 regimens. Before pathways implementation, the participating physicians accounted for 168 distinct chemotherapy regimens for these cancers. By end of year 1, participating practices had reduced the total number to 136, with nearly all of the reduction affecting 10% of the treated population (Figure 3). The following are other behavioral changes adopted by participants: converting brand regimen to generic when equally effective and equitoxic; converting from more expensive to less expensive brand regimens when the same parameters apply; using molecular diagnostics to appropriately guide therapy; appropriate use of supportive care on the basis of evidence; decreasing lines of therapy when evidence is lacking; limiting late lines of therapy to single-agent cytotoxics; using biologics on the basis of labeling rather than irrational exuberance; and as the result of all the above, lower rates of emergency department (ED) and hospital use.

Behavior Change as a Surrogate for Cost Savings

A recent report by the congressional budget office as well as other peerreviewed publications have challenged the savings opportunities in payer-mediated provider  network guidelines.

The absence of observed savings is a significant hurdle to overcome as the stakeholders of healthcare delivery explore solutions to bend the cost curve in cancer care. Although we reported being convinced by Gesme and Wiseman

in our previously reported analyses that our cancer pathways programs can produce meaningful savings, we also recognize the complexity inherent in such analyses. An in-network concurrent provider control group is the ideal comparator for savings. Unfortunately, this control group is flawed by the small numbers of nonparticipants among community providers, which thereby creates wide CIs, the selection

bias inherent in a voluntary participation program (eg, low-cost providers participate, high-cost providers choose not to), and the patient demographic differences among community and academic providers. Concurrent control groups, national or regional, are also compromised, as has been made clear in the wide variations of resource use identified in the Dartmouth Atlas project.

Historical controls are equally contentious, given that oncology in particular is such a dynamic specialty with evolving patterns of care, changing label indications, new drugs and technologies, molecular diagnostics, patent expirations, and so on; all of which contributes to an extent of variables that is nearly impossible to account for in comparative analytics. Finally, data capture problems around hospital-based care as a result of revenue codes and charge bundling and around oral therapeutics distributed among multiple plan vendors leave significant data vacuums. In summation, validated savings with the currently available data from payers and providers is virtually impossible. The authors believe that a sustainable reduction in variance inherently improves quality and cost and can only be achieved by changes in physician behavior.

Compliance Monitoring Challenges and Results

The physician-knows-best approach provided challenges in compliance monitoring. To accurately assess treatment practices, the pathways program relied on data provided by BCBSM, captured through eobONE, or submitted directly by physicians in paper-based forms. Even with this tripartite approach, data capture was incomplete. Revenue codes submitted from hospital settings lacked sufficient detail on the type of treatments received. The full treatment picture for patients with multiple insurance plans was incomplete in the BCBSM data. Data from eobONE included all treatments submitted for reimbursement but lacked information on therapies that were self-administered and obtained by the patient through a pharmacy (eg, oral chemotherapies). Fax data received from physicians provided clarity on oral treatments but were limited by accuracy and completeness of input.

Although we continue to seek solutions to the conundrum of savings measurements in our programs, we believe that behavior change represents an appropriate surrogate that allows payers and providers to collaborate to bend the cost curve while improving quality in cancer care. The costs of cancer care are rapidly increasing and will soon be unsustainable. 1 Many healthcare systems are considering clinical pathways as a method to reduce unnecessary and costly treatment variation; however, the extent to which they can effectively do so relies heavily on design and implementation. Some oncologists have embraced pathways whereas others have resisted, usually as a result of perceived challenges to their autonomy and decision-making ability.

For effective cancer care pathway programs, developing parties and oncology groups must collaborate. Oncologists should participate in the development of pathways they believe reflect appropriate care in their community. Moreover, pathway compliance must be monitored and physician behavior validated to achieve success and best  practice medicine. Feedback with continual discussions should be provided to participating physicians to keep pathwaysmaintained and current. In addition, the mechanism to collect and disseminate this information must be a seamless, effortless process that healthcare providers perceive as unobtrusive to their office work flow. This article outlined a collaborative model between providers and payers to implement a clinical care this database&#151;such as numbers of lines of treatment, brand to generic conversions, use of biologics in multiple lines of therapy, molecular diagnostics to govern care, and acute care interventions in ED and hospital—will be measured in future studies. The results of these analyses will help drive future program design.

We thank Phillips Gilmore Oncology Communications for its technical support.

From Cardinal Health (BAF, JC, SM, JAS), P4 Healthcare, Dublin, OH; Blue Cross Blue Shield of Michigan (JL, JG, DS, TR, TL, TR), Detroit, MI; Physician Resource Management (PS), Novi, MI.

Authors’ Disclosures of Potential Conflicts of Interest

Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a “U” are those for which no compensation was received; those relationships marked with a “C” were compensated. For a detailed description of the disclosure categories, or for more information about ASCO’s conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

Bruce A. Feinberg, Cardinal Health (C); James Lang, Blue Cross Blue Shield of Michigan (C); Thomas Leyden, Blue Cross Blue Shield of Michigan (C); Joseph Cooper, Cardinal Health (C); Thomas Ruane, Blue Cross Blue Shield of Michigan (C); Scott Milligan, Cardinal Health (C); Jeffrey A. Scott, Cardinal Health, P4 Pathways (C).

James Lang, James Grzegorczyk, Thomas Rybarczyk, Thomas Leyden, Thomas Ruane.

Provision of study materials or patients:

Bruce A. Feinberg, Donna Stark, Thomas Rybarczyk, Joseph Cooper, Scott Milligan, Philip Stella, Jeffrey A. Scott.

Bruce A. Feinberg, James Grzegorczyk, Donna Stark, Joseph Cooper, Thomas Ruane, Scott Milligan, Philip Stella, Jeffrey A. Scott.

Bruce A. Feinberg, Joseph Cooper, Scott Milligan, Philip Stella, Jeffrey A. Scott.

Bruce A. Feinberg, DO, 7000 Cardinal Place, Dublin, OH 43017; e-mail: bruce.feinberg@cardinalhealth.com.1. Smith BD, Smith GL, Hurria A, et al: Future of cancer incidence in the United States: Burdens upon an aging, changing nation. J Clin Oncol 27:2758-2765, 2009

2. Elkin EB, Bach PB: Cancer’s next frontier: Addressing high and increasing costs. JAMA 303:1086-1087, 2010

Implementation of Cancer Clinical Care Pathways

1. 2012 Eisai Oncology Digest. Woodcliff Lake, NJ: ReCon Marketing Solutions, LLC; 2012.

Lung cancer remains a most difficult cancer to treat, because of its seemingly intractable progression and the fact that it is usually diagnosed at a late stage. The prevalence of lung cancer, which is directly related to the incidence of tobacco smoking and unacceptable levels of air pollution, continues to challenge scientists and health economists worldwide.

A Quarter-Million Americans to Be Diagnosed This Year

Lung cancer accounts for 14% of all new cases of cancer today, and of the many forms of lung cancer, non&#151;small cell lung cancer (NSCLC) is the most prevalent, accounting for 85% to 90% of all lung cancer cases.

Of patients with NSCLC, adenocarcinomas comprise the greatest proportion (40%), followed by squamous cell tumors (up to 30%) and large-cell tumors (up to 15%), with miscellaneous types comprising the remainder.

According to the American Cancer Society’s latest estimates, lung cancer (all forms) will be diagnosed in 226,000 men and women in 2012, and will result in more than 160,000 deaths&#151;this represents 28% of all yearly cancer deaths.

If diagnosed at the earliest stage (1A), the 5-year survival associated with NSCLC is 49%. Those patients whose lung cancer is classified as stage 2 at the time they are diagnosed have a 30% 5-year survival, and this figure drops precipitously with more advanced disease. Despite major gains in our understanding of how NSCLC develops and spreads, survival gains have been slow and incremental. The best chance of a cure is still surgery, which is most effective in the earliest stages of NSCLC.

Multiple Treatments Available and a Full Pipeline of Targets Await

In an effort to gain a foothold in the war on lung cancer, many approaches to treatment of NSCLC have been tried over the last 2 decades. This has resulted in complex treatment algorithms, as reflected in the National Comprehensive Cancer Network guidelines. Treatment considerations can include surgical resection (with or without preoperative chemoradiation) with lymph-node dissection or sampling and followed by adjuvant treatment (typically radiotherapy and/or chemotherapy [often cisplatin and vinorelbine or etoposide]). For patients with inoperable or recurrent disease, first-line chemotherapy may consist of double treatment (usually cisplatin and another agent); bevacizumab plus chemotherapy; cisplatin/pemetrexed; or a combination of cetuximab, vinorelbine, and cisplatin, all of which is partly based on the specific NSCLC subtype (ie, adenocarcinoma vs squamous cell or large cell). Secondline chemotherapy may add crizotinib, docetaxel, erlotinib, or gemcitabine to the mix of options. In addition to the medications already mentioned, patients with advanced or metastatic NSCLC may also receive carboplatin, ifosfamide, irinotecan, or mitomycin. Treatment recommendations will vary based on a finding of adenocarcinoma or squamous cell carcinoma and on the patient’s performance status rating.

Recent emphasis has been placed on identifying patients who overexpress epidermal growth factor receptor (EGFR). In patients with EGFR overexpression and recurrent or advanced disease, targeted monotherapy with erlotinib, a tyrosine-kinase inhibitor, has been found to offer a 2-month survival advantage over patients receiving placebo.

Cetuximab, the latest EGFR inhibitor used for NSCLC, works by binding to the extracellular domain of EGFR, blocking activation of the EGFR pathway.

Newer treatments are needed to fight this tenacious cancer, as progress in increasing survival in NSCLC has been challenging. Some promise was seen with vascular-disruptive agents (eg, ASA404) and with other tyrosinekinase inhibitors (eg, vandetanib and sorafenib), but the outcomes of these trials have been disappointing.

It may well be that medications such as these are effective in patients with a specific biomarker that has not yet been recognized&#151; that is, some medications are awaiting identification of a patient subpopulation.

Studies of the use of immunotherapy and therapeutic vaccines in NSCLC a marketing partner as clinical trials progress. However, the vaccines, like other modalities in NSCLC, are likely to be used with other therapies. For example, it may be optimal to use therapeutic vaccines in combination with antibodies to amplify the immune response.

This incremental improvement in survival in NSCLC (especially overall survival) has placed payers between the proverbial rock and a hard place. Do they see value in the newer treatments (which are commonly more expensive than older platinum-based therapies), while seeing a limited survival benefit for only a portion of patients? And, it is exceedingly difficult, from the health plan or insurer’s perspective, to restrict cancer therapies shown to have even very limited clinical benefit.

The costs associated with NSCLC can be extensive. In patients with advanced NSCLC (stage IV disease), the average total cost of care was calculated to be $162,134 in a privately insured population, or $10,284 per patient per month. The newer agents (including pemetrexed, biologics, and tyrosine kinase inhibitors) cost an average $10,141 per patient per month (for the duration of their treatments).

As newer agents have been introduced, the cost of treatment for NSCLC has risen. This is likely due to higher prices for new therapies in general and the prevalence of combination regimens in NSCLC. In 2005, the mean drug cost of second-line therapy was $5939; in 2009, it increased to $10,057.

Therefore, payers need to obtain the best value they can from available treatments in NSCLC. New, more effective agents are expected to become available, but one way to increase the value of existing therapies is to better match patients with treatments. Two studies vividly illustrate the point: In one US study of patients receiving second-line therapy for NSCLC, researchers could find no difference in survival outcomes (overall or progression-free survival) among those taking erlotinib, docetaxel, or pemetrexed.

However, in an Italian study, patients with NSCLC who did not express the EGFR mutation had significantly worse progression-free survival (PFS) when they were given the EGFR inhibitor erlotinib compared with docetaxel as second-line therapy.

Furthermore, in a phase III study of an investigational EGFR inhibitor (afatinib), an international team of researchers found a 6.7-month advantage in progression-free survival for patients with the EGFR mutation compared with pemetrexed and cisplatin as first-line therapy.

High levels of ERCC1 overexpression can predict a poor response to platinum-based therapy, but high RRM1 levels are predictive of resistance to gemcitabine-based therapy.

Furthermore, low expression of thymidylate synthase may correlate with higher PFS with pemetrexed in patients with adenocarcinoma- type NSCLC.

Researchers are actively evaluating wide panels of serum biomarkers to better understand which therapies may be more effective in certain patients. For example, bevacizumab has been associated with some benefits in NSCLC, and researchers from Rush University in Chicago tested 72 biomarkers from the sera of 93 patients with advanced NSCLC. Of the patients receiving bevacizumab-containing regimens, those with higher serum levels of PDGF-AB/BB had significantly better PFS and overall survival (OS) than the others.

Indeed, clinical investigations are under way to determine whether gene amplifications or mutations, involving such genes as KRAS, ALK, FGFR1, DDR2, and PIK3CA, to name a few, can predict who will benefit optimally from therapy and even determine which patients with NSCLC have a better prognosis.

Another potentially valuable asset of biomarker identification could be the mediation or avoidance of therapy-associated side effects, which can add significant costs. For example, the occurrence of chemotherapy-associated peripheral neuropathy resulted in $17,344 higher costs compared with those who did not experience peripheral neuropathy.

An important consideration regarding the value of biomarker identification in NSCLC (as well as in most cancers) is the frequency with which the biomarkers appear in the disease. That is, the cost of biomarker identification depends on the cost of the assay to quantify its presence (and of course, the accuracy and sensitivity of the test) and the frequency with which the biomarker can be expected to appear.16 To illustrate, if one were to screen for a biomarker like ALK at an assay cost of $1400 per person, but the biomarker is bevaciexpected to appear in only 2% of the population, screening in all patients with advanced NSCLC for ALK, excluding treatment cost, would be $106,707 per quality-adjusted life-year (QALY). This can drop as low as $4756 per QALY if the biomarker occurs in 36% of patients with NSCLC.

Therefore, it makes the most sense to screen for high-frequency gene mutations or amplifications, assuming a treatment benefits a patient with the biomarker (or possibly works better in those without it).

Two definitive drivers of cost of NSCLC (or of lung cancer in general) are the prevalence of cigarette smoking and its diagnosis in relatively late stages. The vast majority of patients are diagnosed not in stage I, when surgery may be curative, but in stages III or IV, when survival is much lower.

Cigarette smoking (including chronic inhalation of secondhand smoke) is estimated to cause 85% to 90% of all lung cancers.

The remainder of cases are attributed to environmental factors, such as radon, radiation, or asbestos exposure, and diesel exhaust.

Cigarette smoking costs the nation $96 billion annually in direct medical expenditures and $97 billion in lost productivity.

According to an actuarial analysis, exposure to secondhand smoke results in over $10 billion annually in US health expenditures.

The Centers for Disease Control and Prevention found that in 2010, 19.3% of US adults smoked, which represented a decline of 3 million smokers from 2005.

Prevention of NSCLC (or of lung cancer in general) is the favored approach to cost-effective public health; however, smoking in younger people has not decreased substantially. A total of 27.3% of adolescents, teens, and adults reported using tobacco products (including cigarettes, smokeless tobacco, cigars, and pipe tobacco) in 2010.

Lung cancer is most often diagnosed late in the disease course. Identification of cancers earlier in high-risk populations (eg, current smokers) could result in more patients diagnosed with stage 1 NSCLC, with greater chance for cure or longer survival. A recent investigation in the use of spiral-computed tomography (which delivers relatively low doses of radiation compared with conventional scanning) in high-risk patients was found to lower mortality but not necessarily costs.

This should not be surprising: As patients’ tumors are diagnosed early in the course of disease, they may undergo more cycles of chemotherapy and additional therapies in an effort to arrest its spread than a patient whose tumor is identified in stage III or IV. However, the probability for curing these patients with early-stage NSCLC is still greater.

The screening rates for lung cancer are low, either by chest x-ray or lowdose computed tomography (CT) scan. A recent study revealed that only 2.5% of adults underwent a chest x-ray in 2010 specifically to screen for lung cancer, and 1.3% received a low-dose CT examination.

Patients with lung cancer have compounds (volatile organic compounds) in their exhaled breath that differ from those found in healthy individuals. These aromatic compounds are byproducts of the tumor’s metabolism. Hence, these compounds could be used as a biomarker for distinguishing benign from malignant pulmonary nodules. Various tests for analyzing this exhaled air are being explored. One unique idea is to use sniffer dogs; they have been used in other settings to take advantage of their keen olfactory system. Trials have been conducted that confirm sniffer dogs can identify lung cancer from a breath sample.

Along these same lines, researchers at Israel’s Technion Institute are moving forward with the Nano Artificial Nose, which may be able to “smell” lung cancer. It is a breath test that differentiates between benign and malignant pulmonary nodules as well as differentiating between small-cell lung cancer and NSCLC. Some evidence shows that it is also able to identify early cancer from more advanced disease.

Early stage trials demonstrate an accuracy of 80% to 90% in differentiating benign from malignant disease. It also demonstrated 90% accuracy in differentiating the 2 types of cancer as well as the progression of the disease.

Knocking On (or Breaking Down) the Door of Progress

Hope remains that the relatively small gains we make with the completion of each new research study will lead to large gains in prevention and survival in the near future. Perhaps the next 5 years will be key to unlocking the secrets of effectively treating NSCLC.

As in most cancers, prevention represents the best value by far in NSCLC.Earliest possible diagnosis, which offers the best chance for a long remission or cure, can only occur with better compliance with screening guidelines and the use of new diagnostic methods. In terms of active treatment, better targeting of existing, expensive biopharmaceuticals and the introduction of new and novel pipeline products hold the keys to better clinical results and value.

EBO: How does Blue Cross and Blue Shield of Texas determine the value of the targeted lung cancer therapies? Are you using a Pharmacy & Therapeutics or technology assessment committee?

Primarily, we use our medical policy process, which is what we call the formal written documents of benefit coverage based on technology assessment. When technologies are drug related, we bring in pharmacy experts to help us make a coverage determination. Technology assessment tends to be easier with drugs, because we can use FDA approval as a reference point for a specific indication. We also evaluate requests&#151;on a case-by-case basis—for offlabel uses of these drugs.

EBO: Does your plan require that patients must undergo biomarker testing or companion tests before receiving targeted agents, such as Erbitux (cetuximab)? Or, is it sort of really up to the doctors’ discretion?

This raises 2 questions: (1) Do we pay for those kinds of tests? and (2) Do the tests provide information that will improve outcomes? We evaluate biomarker tests on a separate basis. If we decide that a test will/can help improve patient management, we leave it up to the doctors to decide if it’s appropriate for a specific patient.

We have very few prior authorization requirements. We find that when expensive procedures, products, and therapies are being contemplated, physicians tend to ask us to do pre-service review for medical necessity. This tends to work out best for doctors, their patients, and&#151;in a way—for us, because if you can settle the medical necessity for coverage of a service before it is performed and hits our claim system, it is easier to manage. We get many voluntary requests even though we have very few prior authorization requirements.

The Keys to Obtaining Best Value in Non-Small Cell Lung Cancer

Targeting the ALK gene with the oral agent crizotinib (Xalkori) slowed or eliminated signs of tumor growth in pediatric patients with aggressive forms of neuroblastoma, anaplastic large cell lymphoma (ALCL), and inflammatory myofibroblastic tumors (IMTs), according to the results of a phase I study. The research was presented at a press conference held in advance of ASCO 2012.

Crizotinib is a small-molecule inhibitor of ALK and c-Met, and is FDA approved for adults with locally advanced, non&#151;small cell lung cancer that is ALK-positive. The 3 pediatric cancers examined in the trial are associated with mutations in the ALK gene, thus making them susceptible to ALK inhibition. ALCL, a type of non-Hodgkin lymphoma, harbors an ALK mutation in approximately 80% to 95% of tumors. Additionally, half of IMTs and 14% of neuroblastomas are known to contain ALK rearrangements.

A total of 70 children with refractory solid tumors and ALCL were enrolled in the dose escalation and pharmacokinetic trial, but only 42 were evaluable. Patients received one of 6 doses of crizotinib twice daily. Not all participants were required to harbor a known ALK mutation; as such, 19 patients in the neuroblastoma arm had an unknown ALK status.

The most impressive findings from the trial came in the ALCL arm. These 8 patients all had an ALK mutation and were heavily pretreated, with 88% (n = 7) experiencing a complete response to treatment. Patients remained on treatment for as long as 18 months.

“Our trial shows that crizotinib appears to have a high degree of activity in children with anaplastic large cell lymphoma, the majority of which are driven by the ALK oncogene,” said lead author, Yael Mossé, MD, from The Children’s Hospital of Philadelphia, Pennsylvania , who spoke at the ASCO press conference. “A larger anaplastic large cell lymphoma trial is currently in development to move this therapy upfront for newly diagnosed patients.”

Among the 7 patients with IMTs who were enrolled in the trial, most benefited, with results ranging from tumor shrinkage to complete tumor regression. Responses have lasted for up to 2 years, and all patients are still receiving therapy. No available anticancer agents have previously been found to be effective in this disease.

September

Trends in the 2012 Eisai Oncology Digest: Counseling and Communication of Cancer Treatment

Achieving Quality and Containing Cost Through Oncology Pharmacy Management

Treatment and Cost Implications of Pertuzumab

Rationalizing Treatment and Coverage Decisions With Predictive Biomarkers

Implementation of Cancer Clinical Care Pathways

Trends in the 2012 Eisai Oncology Digest: Counseling and Communication of Cancer Treatment

The Keys to Obtaining Best Value in Non-Small Cell Lung Cancer

Crizotinib Active in ALK-Positive Pediatric Cancer

Oncology Leaders Praise Health Law Ruling-With Caveats

Study Supports Feasibility of Routine Molecular Screening of NSCLC in Community Setting

How Can We Get Better Value in End-of-Life Care?

Down the Road for Breast Cancer

How Payers and Oncologists Really Feel About Oncology Pathways

Partnering With a Payer to Develop a Value-Based Medical Home Pilot: A West Coast Practice's Experience

Oncology Patient-Centered Medical Home

Medical Drug Benefit Management in the Pathway Era