, “25 Years of WIRED Predictions: Why the Future Never Arrives,” David Karpf reviewed every issue in chronological order to get a sense of how accurately the magazine had predicted the future.

 He found experts and sages to have a relatively poor track record for predicting what will happen. “The mistake that seems most glaring is the magazine’s confidence that technology and the economics of abundance would erase social and economic inequality,” he wrote.

Karpf’s key finding is worth remembering as we consider the future of cancer care. In a time of unprecedented innovation in oncology therapeutics and genomic diagnostics, it is easy for our excitement at these technologies to obscure our view of the gaps in patient access to equitable cancer care, the challenges of paying for ever more expensive treatments, and

the lack of transparency around care outcomes. As advances in diagnostic and therapeutic cancer care technologies offer promise to patients in need, without an effective system that can deliver them to patients in a sustainable way, there will be no way to ensure that the promise of these advances translates into realty for patients who need them most.

As Karpf realized, technology alone will not save us. The future of cancer care requires a delivery system that fosters greater patient engagement, including more effective cancer screening; more creative and sustainable ways of funding continued advances; sustainable reimbursement models for innovative therapeutics; and the creation of a more patient-centered ecosystem for care delivery that more effectively meets patients’ needs and overcomes barriers to care delivery, including those related to social determinants of health.

, we take the opportunity to both look at the impact of these advances in cancer care and at how our systems of care will need to evolve. Robin Gelburd, JD, president of FAIR Health, reviews claims data to better understand who gets cancer and who is likely to get cancer in the future. In a complementary article, we get a perspective from authors at Mayo Clinic and Exact Sciences on the future of cancer screening. In Andrew Smith’s interview with Professor Andrew Lo, of the MIT Sloan School of Management, we learn of some new models for funding drug innovation that may point to a future in which greater patient needs, particularly among patients with rare tumors, may be addressed through a model that differs from that of traditional pharmaceutical research and development. We also have 2 articles that speak toward how we might meet some of the challenges of the high cost of anticancer drugs. Finally, we get both the perspective of the Community Oncology Alliance and Barbara McAneny, MD, a medical oncologist and the current president of the American Medical Association, on their work to foster more effective ecosystems for delivering cancer care.

At the recent Patient Centered Oncology Care® meeting, several expert participants voiced a common sentiment: As oncologists, we are inherently optimistic about the future. The possibilities for patients with cancer have never been brighter. Innovations and diagnosis and cancer therapeutics have changed the prognosis for many patients with advanced cancers and point toward a future with an even more dynamic pace of innovation. As we work together to navigate the challenges of care cost and create more patient-centric systems for care delivery, I am deeply optimistic that patients and their families will benefit tremendously from these advances. A key part of the mission of 

 is to foster discussions among the many cancer care stakeholders whose coordinated efforts are required to achieve this vision of the future. Throughout the next year, we look forward to bringing more of these conversations to you.

1. Karpf D. 25 years of WIRED predictions: why the future never arrives. 

. September 18, 2018. wired.com/story/wired25-david-karpf-issues-tech-pre- dictions/. Accessed November 28, 2018.

Articles

Evidence-Based Oncology

From the Editor-in-Chief: Why the Future Never Arrives

Community Oncologists Divided on the Value of Biosimilars

During the Community Oncology Alliance (COA) Payer Summit, held October 29-30, 2018, The Center for Biosimilars

 had the opportunity to sit down with several oncologists to discuss their opinions on and experiences with biosimilars.

When asked how he feels about the upcoming availability of anticancer biosimilars as treatment options, Lalan Wilfong, MD, executive vice president of Quality Programs at Texas Oncology, was hopeful. “I think most practices are looking forward to the development of biosimilars, similar to the generic market1 when generics were introduced, that’s when prices actually started falling for cancer therapy,” Wilfong said at the event.

, MD, CEO of Carolina Blood and Cancer Care echoed Wilfong’s statement, but also explained that he believes biosimilars have a central role to play in the US healthcare system as a whole, not just in cancer care. Patel speaks from personal experience; he presented data at ASCO’s Quality Care symposium that found that “7% of total savings of the Oncology Care Model came from switching to biosimilar [granulocyte colony-stimulating factor] G-CSF, [filgrastim]” in his own health system.

However, not all oncologists were in agreement about the value of biosimi- lars. When asked if she believes biosimilars have a role in bringing down drug costs, Kavita Patel, MD, nonresident senior fellow at the Brookings Institution, said, “No. I think that there are limited numbers of biosimilars, and I don’t think that the biosimilars are priced at such a degree that—when you have drugs that cost hundreds of thousands of dollars to millions of dollars&mdash;having a biosim- ilar even for something with a large clinical indication, it’s like a fraction of the overall drug spend.”

Although biosimilars have the potential to bring down costs, she conceded, some factors in the marketplace need to be addressed first before they begin generating significant savings.

“I think we need more biosimilars, which the FDA has signaled, and we need more biosimilars that are priced at such a delta to make an appreciable difference,” she said. “There are some pretty ‘hot’ oncology drugs that have a biosimilar available, but then the way the practice might have already set up their pharmacy or their network, they’ve already kind of locked in to certain manufacturers, making the biosimilar less attractive.”

One specific need reiterated by each oncologist was that, in order for physicians to feel more comfortable prescribing biosimilars in their own practice, education on the safety and efficacy data associated with the products is key going forward.

1. Cate Lockhart, PharmD, PhD: similarities between biosimilars and generics. The Center for Biosimilars

 website. www.centerforbiosimilars.com/interviews/cate-lockhart-pharmd-phd-similarities-between-biosimilars-and-generics. Published June 25, 2018. Accessed November 9, 2018.

Biosimilars Can Play a Key Role in Value-Based Care, Review Says

2. Dr Kashyap Patel: biosimilars and value. The Center for Biosimilars® website. www.centerforbiosimilars.com/ interviews/dr-kashyap-patel-biosimilars-and-value. Published December 7, 2017. Accessed November 9, 2018.

Given the high burden associated with cancer in the senior population, and given the increasingly high cost of cancer care, there is a growing interest in value-based oncology care payment models, particularly within CMS.

, and colleagues, provides an overview of value-based care models and discusses the role of biosimilars in meeting these models’ objectives.

, notes that US spending on cancer care grew from $27 billion in 1990 to $124 billion in 2010, with spending levels expected to reach $157 billion by 2020. Globally, spending on oncology and supportive care reached $100 billion in 2014. Among the fastest-growing drug classes in oncology are monoclonal antibodies—many of which are targeted by biosimilar developers&mdash;which account for 35% of US oncology spending.

To help address skyrocketing costs, CMS has developed value-based care programs that reward providers with incentives for improving the quality of care they provide to Medicare beneficiaries. These programs seek to move away from the fee-for-service (FFS) model that incentivizes high-quantity (although not necessarily high-quality) care.

In 2016, CMS implemented the Quality Payment Program, which offers payment to providers either through the Merit-based Incentive Payment System or through Advanced Alternative Payment Models, one of which is the Oncology Care Model (OCM).

The OCM is a voluntary program that seeks to provide higher-quality care at the same or lower cost to Medicare than traditional FFS payments. The OCM links payments to provider performance based on meeting quality metrics and making practice reforms.

Biosimilar therapies offer increased affordability and access—as well as improved outcomes and improved health-related quality of life&mdash;to patients treated in the OCM model; using lower-cost biosimilar granulocyte colony-stimulating factor therapies,3 for example, can reduce the incidence of neutropenia, allowing for increased dose administration of patients’ primary treatments and improved survival.

Not only may biosimilars, themselves, be offered at more affordable prices than biologics—as has been demonstrated in experience with biosimilar filgrastim&mdash;but they also may drive down overall prices in a given class as a result of market competition, producing substantial US cost savings. These savings, which have the potential to grow with upcoming availability of biosimilar epoetin alfa and biosimilars of targeted therapies, could help physicians to meet the OCM objective of improving patient care while reducing costs.

However, write Patel and colleagues, “Realization of cost savings possible from biosimilars...will require that biosimilars are utilized.” Current gaps in physician education4 on biosimilars have limited the use of these agents, making the need for provider education all the more pressing.

1. Patel KB, Arantes LH Jr, Tang WY, Fung S. The role of biosimilars in value-based oncology care. 

. 2018;10:4591-4602. doi: 10.2147/CMAR.S164201.

2. Davio K. Patient-administered biosimilar and follow-on filgrastim pose opportunity for savings. The Center for Biosimilars® website. www.centerforbiosimilars.com/news/patientadministered-biosimilar-and-followon-filgrastim-pose-opportunity-for-savings. Published August 13, 2018. Accessed November 1, 2018.

3. Davio K. Despite educational efforts, providers still lack knowledge on biosimilars. The Center for Biosimilars® website. www.centerforbiosimilars.com/conferences/acr-2018/despite-educational-efforts-providers-still-lack-knowledge-on-biosimilars. Published October 18, 2018. Accessed November 1, 2018.

As Reassuring Data on Anticancer Biosimilars Grow, ESMO Ups Its Biosimilar Education

The European Society for Medical Oncology (ESMO) 2018 Congress, held October 19-23, 2018, in Munich, Germany, featured multiple presentations on biosimilars in oncology, all of which are contributing to the body of evidence that points to the safety and efficacy of these products.

 closely investigated the efficacy of the trastuzumab biosimilar SB3, approved in the European Union and sold as Ontruzant, with the reference product in patients with early breast cancer (EBC).

The study enrolled 800 total patients, with 402 given the biosimilar and 398 given the reference trastuzumab. Patients were treated for 8 cycles concurrently with chemotherapy. Patients underwent surgery, and then 10 more cycles of SB3 or the reference.

The primary endpoint was breast pathologic complete response (bpCR) rate, which was measured at 51.7% for SB3, and at 42.0% for the reference, with an adjusted difference of 10.7% (95% CI, 4.13-17.26).

Overall, the researchers found that the analysis results of bpCR, total pathologic response rate, and overall response rate leaned toward greater efficacy in patients treated with SB3 compared with the reference product.

 researchers conducted a systematic literature review to examine whether demonstrating bioequivalence in terms of efficacy is different in EBC versus metastatic breast cancer (MBC) when patients are treated with a biosimilar trastuzumab, Ogivri (trastuzumab-dkst), versus the reference product.

In total, researchers identified 8 phase 3 clinical trials for 6 proposed biosimilars. Of these, 4 were conducted in EBC, and 4 were in MBC. In all trials, the proposed biosimilar was found to be equivalent to the reference in terms of efficacy. Two biosimilars showed equivalent efficacy in both the EBC and MBC settings.

Regardless of clinical setting, all biosimilars analyzed demonstrated equivalent efficacy to reference trastuzumab.

Despite such reassuring data for biosimilars, however, many stakeholders have noted that lack of provider education on biosimilars is holding back progress with uptake of these products.

Concurrently with the meeting, ESMO published a new paper

 on the integration of biosimilars into routine oncology practice. The paper reports that, when questioned about their knowledge of and comfort with biosimilars, many oncologists exhibited only “moderate confidence” in their understanding of key concepts related to biosimilar drug development and use. Nearly 87% of respondents said that they need more educational activities on the subject.

The paper also found that extrapolating the use of a biosimilar to all indications approved for the reference product seemed to be the most common misunderstanding among physicians, nurses, and patients alike.

“It is a very difficult concept to explain outside of the regulatory setting,” said Elena Wolff-Holz, MD, of the European Medicines Agency. “This is what educational activities should focus on—not just for oncologists, but for all healthcare professionals and for patients,” said Josep Tabernero, MD, PhD, MSc, president of ESMO.

Among ESMO’s attempts to provide such education are its position paper on using biosimilars and its multistakeholder discussion forums held both at this year’s congress and previously at the 2017 meeting.

1. Castan JC, Pegram M, Pivot X, et al. Subgroup analyses of efficacy from a phase III study comparing SB3 (trastuzumab biosimilar) with reference trastuzumab in early breast cancer patients. Presented at: European Society for Medical Oncology 2018 Congress; October 19-23, 2018; Munich, Germany. Abstract 217P. https://cslide. ctimeetingtech.com/esmo2018/attendee/confcal/session/calendar?q=217P&c=abs.

FDA Approves Celltrion's Rituximab Biosimilar, Truxima

2. Rugo HS, Curigliano G, Cardoso F, et al. Settings-based efficacy comparison of trastuzumab biosimilars in breast cancer: a systematic literature review. Presented at: European Society for Medical Oncology 2018 Congress; October 19-23, 2018; Munich, Germany. Abstract 324P. https://cslide.ctimeetingtech.com/esmo2018/attendee/ confcal/session/calendar?q=217P&c=abs. 3. Wolff-Holz E, Garcia Burgos J, Giuliani R, et al. Preparing for the incoming wave of biosimilars in oncology. ESMO Open. 2018;3(6):e000420. doi: 10.1136/esmoopen-2018-000420.

The FDA has approved Celltrion and Teva’s rituximab biosimilar, Truxima (rituximab-abbs). The biosimilar, referencing Rituxan, has been approved to treat adults with CD20-positive, B-cell non-Hodgkin lymphoma (NHL) either as monotherapy or in combination with chemotherapy.

Like its reference product, Truxima has a label that carries a boxed warning alerting providers and patients to the risk of fatal infusion reactions, skin and mouth reactions, hepatitis B reactivation, and a rare but serious brain infection.

In a statement, FDA Commissioner Scott Gottlieb, MD, hailed approval of the drug as an example of the success of the agency’s Biosimilar Action Plan. “The Truxima approval is our third biosimilar approval in the past month. The growing pipeline of biosimilars is encouraging,” he said. “We’re seeing more biosimilar drugs gain market share as this industry matures. We’ll continue to make sure biosimilar medications are evaluated efficiently through a process that makes certain that these new medicines meet the FDA’s rigorous standards for approval.”

Truxima’s approval follows a unanimous recommendation of approval by the FDA’s Oncologic Drug Advisory Committee (ODAC) in October 2018. In a vote on whether the totality of the evidence supported the licensure of the biosimilar, all 16 committee members voted yes, for reasons some voters enumerated as “overwhelming biosimilarity and clinical trial evidence” that “really sealed the deal.”

The committee heard a review of data presented from various speakers, including advisory officials for the FDA who analyzed the drug’s data prior to the presentation. According to the FDA, although there were minor differences in clinically inactive compounds, the totality of the evidence suggested Truxima is highly similar to the reference product with no clinically meaningful differences.

Notably, while the reference rituximab also carries indications for inflammatory diseases including rheumatoid arthritis, Celltrion sought approval only for indications in oncology; when ODAC members asked about the reasoning behind only seeking an indication in NHL, a Celltrion representative stated that “We are only seeking approval in 3 [NHL] indications given the patent and exclusivity landscape at this time.”

Truxima, which is also approved and widely used in the European Union, is the 15th biosimilar, and the first rituximab biosimilar, approved by the FDA.

1. FDA approves first biosimilar treatment for adults with non-Hodgkin’s lymphoma [press release]. Silver Spring, MD: FDA newsroom; November 28, 2018. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ ucm627009.htm. Accessed November 29, 2018.

2. DiGrande S. ODAC unanimously recommends Celltrion’s biosimilar for rituximab for FDA approval. The Center for Biosimilars

 website. centerforbiosimilars.com/news/odac-unanimously-recommends-celltrions-biosimi- lar-rituximab-for-fda-approval. Published October 10, 2018. Accessed November 29, 2018.

Biosimilars Updates

Tisagenlecleucel's High Price Aligns With Its Benefit in Pediatric B-ALL, Study Results Find

Despite the high cost of tisagenlecleucel (Kymriah), the chimeric antigen receptor (CAR) T-cell therapy to treat pediatric patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), the benefits of the treatment support the price, according to research in 

A group of researchers that included individuals from the Institute for Clinical and Economic Review compared life-years gained, quality-adjusted life-years (QALYs) gained, and incremental costs per life-year and QALY gained of tisagenlecleucel with the chemoimmunotherapeutic agent clofarabine (Clolar).

Although research has shown that tisagenlecleucel has higher rates of re- sponse, event-free survival, and overall survival compared with other therapies used to treat this population, the “follow-up for patients receiving tisagenlecleucel is limited, with a maximum duration of less than 4 years; therefore, uncertainty remains around its long-term benefit,” the authors explained.

They used a decision analytic model to extrapolate trial evidence from 3 studies and collected all costs and outcomes expected from the CAR T-cell therapy. They analyzed the therapy from a payer perspective and estimated outcomes over a patient’s life.

They found that more than 40% of patients who initiated tisagenlecleucel would become long-term survivors or would be alive and responding to treat- ment after 5 years. In comparison, only 10% of patients who receive clofarabine would be long-term survivors.

The total discounted cost of tisagenlecleucel was $667,000, with 10.34 discounted life-years gained and 9.28 QALYs gained. Clofarabine had a total discounted cost of $337,000, with 2.43 discounted life-years gained and 2.10 QALYs gained. The approximate incremental cost-effectiveness ratio of tisagenlecleucel versus clofarabine was $42,000 per life-year gained and $46,000 per QALY gained.

The researchers ran multiple scenarios to account for long-term relapse and survival, and the cost-effectiveness estimates ranged from $37,000 to $77,500 per QALY gained. They concluded that tisagenlecleucel is priced in alignment with its benefits over a patient’s life.

“Financing cures in the United States is challenging owing to the high up-front price, rapid uptake, and uncertainty in long-term outcomes; however, innovative payment models are an opportunity to address some of these challenges and to promote patient access to novel and promising therapies,” the authors wrote.

Whittington MD, McQueen RB, Ollendorf DA, et al. Long-term survival and value of chimeric antigen receptor T-cell therapy for pediatric patients with relapsed or refractory leukemia [published online October 8, 2018]. 

Three Genetic Types Drive Higher Prevalence of Multiple Myeloma in African Americans

Multiple myeloma (MM) occurs 2 to 3 times more frequently in Americans of African descent than in Americans of European descent, and a new study

 has identified 3 gene types that account for this disparity.

, demonstrated that the disparity is largely driven by disparities in the occurrence of the t(11;14), t(14;16), and t(14;20) subtypes of MM.

“We sought to identify the mechanisms of this health disparity to help us better understand why myeloma occurs in the first place and provide insight into the best forms of therapy,” Vincent Rajkumar, MD, a hematologist at Mayo Clinic and senior author of the study, said in a statement.

The researchers studied 881 patients with monoclonal gammopathies. Whereas previous research into disparities in prevalence of disease has relied on self-reported race, this study identified the ancestry of patients through DNA sequencing. Self-reported race can result in bias, but the DNA sequencing allowed researchers to determine ancestry more accurately, Rajkumar said.

In the entire cohort, the median African ancestry was 2.3%, the median European ancestry was 64.7%, and the median Northern European ancestry was 26.6%. To better observe differences in the prevalence of MM subtypes, the authors separated the cohort into the most extreme populations with regard to African ancestry.

“Although many individuals in the US are of mixed ancestry, ancestral characterization of patient cohorts is required to fully understand how the role of human genetic variation associated with ancestry impacts health disparities,” the authors wrote.

They found that the probability of having 1 of the 3 subtypes associated with higher risk of MM was significantly greater in the 120 individuals who had at least 80% African ancestry compared with the 235 individuals who had less than 0.1% African ancestry.

 has shown that despite being more likely to be given a diagnosis of MM, African Americans are underrepresented in MM disease research. As a result, improved overall survival for MM has largely been observed in Caucasian patients.

“There are efforts to enroll more minorities in clinical studies, and this is important,” Rajkumar said. “However, it is equally, if not more important, to determine the mechanisms of racial disparities in terms of why cancers occur more often in certain racial groups. Our findings provide important information that will help us determine the mechanism by which myeloma is more common in African Americans, as well as help us in our quest to find out what causes myeloma in the first place.”

1. Baugh LB, Pearce K, Larson D, et al. Differences in genomic abnormalities among African individuals with monoclonal gammopathies using calculated ancestry. 

. 2018;8(10):96. doi: 10.1038/s41408-018-0132-1.

2. Dangor J. Mayo Clinic researchers identify gene types driving racial disparities in myeloma [press release]. Rochester, MN: Mayo Clinic; newsnetwork.mayoclinic.org/discussion/mayo-clinic-researchers-identify-gene-types-driving-racial-disparities-in-myeloma/. Accessed October 15, 2018.

3. Manoklovic A, Christofferson A, Liang WS, et al. Comprehensive molecular profiling of 718 multiple myelomas reveals significant differences in mutation frequencies between African and European descent cases. 

 2017;13(11):e1007087. doi: 10.1371/journal.pgen.1007087.

Medical World News: Clinical Updates

FDA Approves Cemiplimab-rwlc to Treat Second Most Common Skin Cancer

The FDA has approved the immune checkpoint inhibitor cemiplimab-rwlc, to be sold as Libtayo, for the treatment of metastatic cutaneous squamous cell carcinoma (CSCC) or in patients with locally advanced CSCC who are not candidates for curative surgery or curative radiation.

CSCC is the second most common form of skin cancer and is responsible for nearly 7000 deaths each year in the United States. To date, the cancer accounts for an estimated 20% of all skin cancers in the United States, with the number of patients with the disease expected to rise on an annual basis.

Developed in conjunction by Regeneron Pharmaceuticals and Sanofi, cemiplimab-rwlc is a monoclonal antibody that targets the immune checkpoint receptor PD-1. According to Regeneron, this is the first and only treatment specifically approved and available for advanced CSCC in the United States.

The “FDA decision is great news for patients with advanced CSCC who previously had no approved treatment options....Libtayo is an important new immunotherapy option for US physicians to help address a significant unmet need in this patient group,” said Michael R. Migden, MD, lead investigator in the CSCC clinical program and professor in the departments of Dermatology and Head and Neck Surgery at The University of Texas MD Anderson Cancer Center.

Cemiplimab-rwlc was evaluated under the FDA’s priority review pathway and was granted breakthrough therapy designation status for advanced CSCC in 2017. The recommended dosage of cemiplimab-rwlc is 350 mg administered as an intravenous infusion over 30 minutes every 3 weeks, until disease progression or unacceptable toxicity.

In the United States, the wholesale acquisition cost of the treatment is $9100 per 3-week treatment cycle; however, Regeneron and Sanofi noted that “the actual costs to patients are generally anticipated to be lower, as the list price does not reflect insurance coverage, copay support, or financial assistance from patient support programs.”

“In the United States, CSCC accounts for 1 in 5 skin cancers, and the number of new diagnoses is increasing. We believe Libtayo has the potential to make a difference for US patients with advanced CSCC, as it helps to fill a critical gap in treatment options,” said Olivier Brandicourt, MD, CEO of Sanofi.

FDA Gives Speedy Approval to Brentuximab Vedotin for Peripheral T-cell Lymphoma

1. FDA approves Libtayo (cemiplimab-rwlc) as first and only treatment for advanced cutaneous cell carcinoma [press release]. Tarrytown, NY, and Paris, France: PR Newswire; September 28, 2018. prnewswire.com/news-releases/ fda-approves-libtayo-cemiplimab-rwlc-as-first-and-only-treatment-for-advanced-cutaneous-squamous-cell-carcino- ma-300721188.html. Accessed October 15, 2018.

The FDA announced recently that it expanded the approved use of brentuximab vedotin (Adcetris) in combination with chemotherapy for adult patients with certain types of peripheral T-cell lymphoma (PTCL), using a new review process designed to increase efficiency.

It is also the first FDA approval for the treatment of newly diagnosed PTCL. PTCLs are rare, fast-growing non-Hodgkin lymphomas that develop from T-cells, which spread quickly and are hard to treat. T-cell lymphomas account for between 10% and 15% of all non-Hodgkin lymphomas, according to the Leukemia and Lymphoma Society.

The pilot program under which the drug was approved, Real-Time Oncology Review (RTOR), allows the FDA to review much of the data after the clinical trial results become available and before the information is formally submitted to the FDA. The pilot focuses on early submission of data that are most relevant to assessing the safety and efficacy of a product.

The approval of brentuximab vedotin for PTCL is the fourth time the RTOR has been used, according to an FDA spokesperson.

“When the sponsor submits the completed application, the review team will already be familiar with the data and be able to conduct a more efficient, timely, and thorough review,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products, in a statement.

Brentuximab vedotin is an antibody drug conjugate. Earlier this month, an analysis found that it was cost-effective

 when combined with chemotherapy as frontline treatment for stage III or IV classical Hodgkin lymphoma.

The new approval was based on a clinical trial of 452 patients with certain PTCLs who received either brentuximab plus chemotherapy or a standard chemotherapy (CHOP) as first-line treatment. Progression-free survival was significantly longer (hazard ratio, 0.71; P = .01) in the brentuximab arm (median = 48 months vs 21 months with CHOP). Overall survival and overall response rates were also significantly better in the brentuximab arm.

The drug, sold by Seattle Genetics, had also received priority review and breakthrough therapy designation.

“By participating in the FDA’s Real-Time Oncology Review process and working closely with the FDA, we are now able to make the Adcetris regimen available to previously untreated patients with CD30-expressing PTCL in an unprecedented less than 2 weeks after submission of our supplemental BLA,” said Clay Siegall, PhD, the firm’s president and chief executive officer of Seattle Genetics, in a statement.

The most common adverse effects of brentuximab plus chemotherapy included peripheral neuropathy, nausea and vomiting, diarrhea, low white blood cell counts, fatigue, mouth sores, constipation, hair loss, fever, and anemia.

1. FDA approves first-line treatment for peripheral T-cell lymphoma under new review pilot [press release]. Washington, DC: FDA; November 16, 2018. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm626079. htm?. Accessed November 16, 2018.

2. Caffrey M. Authors find brentuximab vedotin cost-effective for treatment of advanced Hodgkin lymphoma. 

 website. www.ajmc.com/newsroom/authors-find-brentuximab-vedotin-costeffective-for-treatment-of-advanced-hodgkin-lymphoma. Published October 31, 2018. Accessed November 16, 2018.

3. Seattle Genetics announces FDA approval of ADCETRIS® (brentuximab vedotin) in combination with chemo- therapy for adults with previously untreated systemic anaplastic large cell lymphoma or other CD30-expressing peripheral T-cell lymphomas [press release]. Bothell, WA: November 16, 2018. www.businesswire.com/news/ home/20181116005332/en/Seattle-Genetics-Announces-FDA-Approval-ADCETRIS®-Brentuximab. Accessed November 16, 2018.

New Melanoma Guidelines Identify Recommended Treatments, Weigh In on Genetic Testing

New guidelines released by the American Academy of Dermatology (AAD) will help physicians provide the best treatment for more than 1 million Americans living with melanoma, the deadliest form of skin cancer. The guidelines were published1 on Thursday, November 1, in the 

Journal of the American Academy of Dermatology

“Guidelines of care for the management of primary cutaneous melanoma” outlines best practices for treating the disease and was developed by a work group of dermatologists, oncologists, and other experts.

“Melanoma is the deadliest form of skin cancer, and we hope these guide- lines will help dermatologists and other physicians enhance their delivery of life-saving treatment to patients,” board-certified dermatologist Susan M. Swetter, MD, FAAD, co-chair of the work group that developed the guidelines, said in a statement.

 “In order to provide the best possible resource for practitioners, we reviewed the latest scientific data and addressed certain topics that weren’t covered in the AAD’s previous melanoma guidelines.”

Although melanoma is the deadliest skin cancer, current treatments are curative if the disease is detected early enough. The 5-year survival rate is 99% if melanoma is detected early and treated before it spreads to the lymph nodes.

The guidelines review biopsy techniques for lesions suggestive of melanoma; histopathologic interpretation of cutaneous melanoma; use of laboratory, molecular, and imaging tests, as well as follow-up for asymptomatic patients; treatment recommendations, including surgical and nonsurgical options; and the latest data regarding pregnancy and melanoma, genetic testing, and management of toxicities related to novel targeted agents and immunotherapies.

According to the guidelines, patients with a family history of melanoma should receive education and counseling regarding their genetic risk, but formal genetic testing may not always be appropriate. The guidelines recommend that genetic testing be considered on an individual basis after counseling.

Surgical excision is identified as the gold standard of treatment, but it is noted that Mohs surgery or other forms of staged excision may be considered for certain subtypes. Topical therapy or traditional radiation may be considered as second-line therapy in cases in which surgery is not possible. However, because of a lack of evidence, the guidelines do not recommend electronic brachytherapy.

“The guidelines development process included patient advocate and community dermatologist input, and the resulting document emphasizes the importance of the doctor—patient dialogue in all aspects of melanoma management,” said board-certified dermatologist Hensin Tsao, MD, PhD, FAAD, co-chair of the guidelines work group. “Every case is unique, so physicians should work with their patients, and other specialists if necessary, to explain the available options and determine the best possible treatment plan for each patient.”

1. Swetter SM, Tsao H, Bichakjian CK, et al. Guidelines of care for the management of primary cutaneous melanoma. [published online November 1, 2018]. 

2. American Academy of Dermatology releases guidelines for melanoma treatment [press release]. Rosemont, IL: American Academy of Dermatology; November 1, 2018. www.aad.org/media/news-releases/melanoma-guidelines. Accessed November 1, 2018.

Pembrolizumab Plus Chemotherapy Approved to Treat Metastatic Squamous NSCLC

 pembrolizumab (Keytruda) in combination with carboplatin and paclitaxel or nab-paclitaxel for the first- line treatment of patients with metastatic squamous non—small cell lung cancer (NSCLC).

The approval was based on findings from the KEYNOTE-407 trial, a randomized, double-blind, multicenter, placebo-controlled study that investigated the efficacy of the combination treatment in patients with metastatic squamous NSCLC regardless of tumor PD-L1 expression. Patients were randomized to receive pembrolizumab 200 mg and carboplatin every 3 weeks for 4 cycles, plus paclitaxel every 3 weeks for 4 cycles or nab-paclitaxel on days 1, 8, and 15 of every 3-week cycle for 4 cycles, followed by placebo every 3 weeks.

The trial found that pembrolizumab in combination with chemotherapy significantly improved overall survival and reduced the risk of death by 36% compared with chemotherapy alone (hazard ratio = 0.64 [95% CI, 0.49, 0.85]; 

“Today’s approval expands our current lung cancer indications to include combination treatment in patients with squamous cell carcinoma, a type of lung cancer that is particularly difficult to treat,” said Roger M. Perlmutter, MD, president of Merck Research Laboratories.

The safety of the combination treatment was investigated in 101 patients at the first interim analysis of the trial. The most frequent (≥2%) serious adverse effects were febrile neutropenia (6%), pneumonia (6%), and urinary tract infection (3%).

“With this important approval, more patients will have the opportunity to benefit from immunotherapy,” said Balazs Halmos, MD, director of the multidisciplinary Thoracic Oncology Program at the Montefiore Einstein Center for Cancer Care.

This approval is the first time an anti-PD-1 treatment regimen was approved as a first-line treatment of squamous NSCLC regardless of tumor PD-L1 expression. Due to this newly approved treatment option, all appropriate patients with metastatic squamous NSCLC, as well as appropriate patients with metastatic nonsquamous NSCLC and no EGFR or ALK genomic tumor mutations, are now eligible for the pembrolizumab combination treatment as their first-line treatment option.

1. FDA approves Merck’s KEYTRUDA (pembrolizumab) in combination with carboplatin and either paclitaxel or nab-pacl- itaxel for the first-line treatment of patients with metastatic squamous non-small cell lung cancer (NSCLC) [press release]. Kenilworth, NJ: Merck; October 30, 2018. www.businesswire.com/news/home/20181030006098/en/FDA-Approves-Mer- ck%E2%80%99s-KEYTRUDA%C2%AE-pembrolizumab-Combination-Carboplatin. Accessed November 1, 2018.

Medical World News: Regulatory Updates

If physicians can demonstrate they delivered good care, but the patient is left feeling unhappy, what does that tell us about quality?

According to Ana Maria Lopez, MD, MPH, vice chair of medical oncology and chief of the New Jersey Division of the Sidney Kimmel Cancer Center at Thomas Jefferson University

in Philadelphia, Pennsylvania, it may mean that physicians are using the classic value equation of quality over cost—although an update would factor in customer service.

Lopez led the discussion at the Philadelphia meeting of the Institute for Value-Based Medicine®, an initiative of 

, which also featured Kashyap Patel, MD, president and CEO, Carolina Blood and Cancer Care Associates (CBCCA); Michael Ruiz de Somocurcio, vice president for payer and provider collaboration at New Jersey-based Regional Cancer Care Associates (RCCA); and Valerie P. Csik, MPH, CPPS, project director for practice transformation, Sidney Kimmel Cancer Center at Thomas Jefferson University.

According to Lopez, it’s important to ask how cost is defined. What factors are considered? Before service was part of the equation, she said, sometimes “patients were still not happy with the care they were receiving, although we could say demonstrably that it was quality care.”

From the perspective of a physician, the things that mattered— improved clinical indicators, fewer adverse effects&mdash;might not be the things that mattered to patients when they were asked. Often, patients being treated for cancer mentioned things that had nothing to do with their medical care: less time waiting, no problems parking the car, good food in the cafeteria.

As an oncologist, Lopez said, “That has nothing to do with me and quality care, but it has to do with quality of life. And we have the data that improvements in quality of life improve outcomes.”

So, as the population ages, and more people receive a cancer diagnosis—as the disease is diagnosed earlier and treatment costs rise because patients live with the disease for longer periods&mdash; quality of life and patient experiences are rising on the radar. If a patient has a rough time parking every time they come to the clinic, and has checkups every 3 to 6 months for several years, that’s a problem.

What can be done? Lopez said the future lies in integrated practice units, which identify conditions and map out the delivery process as far out as possible. “When you do that, you realize care crosses department lines and service lines, and really needs lots of coordination,” she said. Integrated care allows the health system to ensure that the right care is delivered to the right patient at the right location. A single electronic health record (EHR) is key to a better experience.

It’s also important to help the patient become more effective and responsible for their own care, Lopez said. “This really is a partnership,” she said. “We really want to engage the patient, so they can be a part of this experience.”

Using metrics to measure quality, service, and cost—and to reward innovation&mdash;will require that health systems do what’s in the patient’s best interest, even if it sometimes means competitors within a given market work together, Lopez said. But as practices in the Oncology Care Model (OCM) have seen, when clinicians get the opportunity to see how they compare with their peers, they will say, “I don’t want to be the most expensive person.”

Pathways help decrease variability and cost, she said; the adherence target should be in the range of 70% to 85%, so there is allowance for individual circumstances and adaptation to new knowledge. Health systems must ask what processes their pathways use to incorporate innovation.

But Lopez offered a word of caution about metrics.

“Often,” she said, “we measure what is easy and most accessible, and that may not be what’s giving us the most value.”

Better Patient Access: the "Lowest-Hanging Fruit"

Some practices in the OCM have struggled to achieve savings, but CBCCA isn’t one of them. Patel presented data showing that the relatively small oncology/hematology practice of 5 oncologists and 1 mid-level practitioner has seen success under the model. After up front investments of $715,000 including capital costs on technology, the practice is on track to achieve annualized savings of $550,000, while the savings for Medicare are $1.08 million.

Patel insists there’s no hidden formula. “The one thing that helped us the most was expanded access,” he said. By keeping 2 appointment slots open each day for walk-ins or same-day patients, and by encouraging them to simply come in or use an urgent care center instead of the emergency department (ED), the practice has not only saved money but improved quality of life—for both patients and the doctors.

“We’ve reduced calls from 10 every night to 1 to 2 every night,” Patel said. “It’s not rocket science. See the patients when they need to be seen.”

The practice saves money another way: Patel and his fellow oncologists evaluate the OCM feedback reports themselves, making adjustments instead of using consultants, as larger practices do.

Patel even makes some home visits, especially for patients who live in remote areas. It’s all part of embracing what’s required in the OCM, which calls for reducing the burden on the patient.

At the start, CBCCA leaders asked the staff for ideas on how to fully engage patients.

“They asked, ‘Can we have a holistic approach?’” Patel said that besides things like upgraded computerized axial tomography scan technology, employees developed an education booklet with staff photos so patients know everyone’s name and created a calming garden and fountain within the facility. One physician serves as a voluntary chaplain, and there is great attention to spirituality and end-of-life care.

Physicians also have embraced the use of biosimilars, especially filgrastim-sndz (Zarxio), to promote growth of neutrophils and prevent infection. Patel said the practices has not experienced resistance from patients to using biosimilars.

Their success has not gone unnoticed. The Center for Medicare and Medicaid Innovation is working with CBCCA to help it become one of the first oncology practices to take on 2-sided risk, and Patel is exploring innovative reinsurance ventures with other practices around the country that would make this financially feasible.

In Patel’s view, it all comes back to the basics. “It’s about instructing the patient to come to the office when they need to,” he said. “Improving access is probably the lowest hanging fruit that our system has not emphasized.”

RCCA operates in 4 states and treats 33% of all cancer cases in New Jersey. Ruiz de Somocurcio said this means dealing with a variety of payers and value-based care initiatives, from the

OCM to bundled-payment programs with commercial payers, the largest being Horizon Blue Cross Blue Shield of New Jersey.

“When you’re in these programs, it’s absolutely critical that you work with community physicians outside of your walls,” he said. These are all total-cost-of-care programs, so the oncologist is respon- sible whether the patient also has diabetes “or even if they get hit by a car.” Figuring out how to find value by working with the independent physician is key, “based on site of service alone,” Ruiz de Somocurcio said. And health plans have been receptive.

As he explained, value-based care in oncology isn’t happening in a vacuum. Mergers between Cigna and Express Scripts, Aetna and CVS, and collaborations among Amazon, JP Morgan Chase, and Berkshire Hathaway are just some examples of healthcare realignment. “That’s going to impact choices,” Ruiz de Somocurcio said.

While the market shifts toward downside risk, he said RCCA is determined to get there ahead of the curve, and things seem to be moving toward an oncology medical home model, with quality metrics that focus on advanced care planning, pain, and management of depression, alongside cost metrics that target ED and inpatient admissions, as well as end-of-life care.

Data sharing is key. To get data, an entity must give it as well. But without data, taking on additional risk makes little sense. Doing so has revealed that the highest-cost patient isn’t just the patient with cancer; rather, it’s the patient with existing comorbidities, like congestive heart failure, who develops cancer. Scrutinizing data has also shown:

Post acute care costs are 2 times higher than national averages compared with other OCM practices.

New Jersey admits too many patients with cancer who appear at the ED, and this is consistent across all hospitals.

End-of-life care needs improvement, particularly with physician buy-in.

Meanwhile, providers who are not in the OCM are adapting the impact of the Merit-based Improvement Payment System. CMS, Ruiz de Somocurcio said, “is creating winners and losers,” which will further drive consolidation.

Csik gave an overview of the many initiatives attempted over the past decade to move reimbursement away from fee-for-service to outcomes-based models. Although the Trump administration initially balked at continuing some value-based models that started under its predecessors, that seems to be shifting, with HHS Secretary Alex Azar announcing November 8, 2018, that a radiation oncology model would be coming shortly.

It’s important to understand how different stakeholders define value. Patients want to know that the doctor they are seeing is in network. Physicians want a streamlined referral process. Payers want cost control.

Csik described an approach to practice transformation that included many of the same elements that Patel and Ruiz de Somocurcio included: having clearly defined goals, investing in technology, minimizing clinical variation, using data to promote accountability, reducing trips to the ED and unnecessary hospitalization, and improving end-of-life care.

The key to it all, she said, “is the commitment— staying the course. I think all of us that have participated in the Oncology Care Model have recognized the many shifts and changes that CMS has made in the last 2-and-a-half plus years in that program and they will continue to make in the remaining few years of the program. That agility is something that’s really critical in terms of our ability to sustain progress.”

Early efforts at value-based care, “heightened our awareness but didn’t really give us a framework,” Csik said. The OCM did just that and required Jefferson to learn and adapt to the data it was receiving.

Accelerating the process will happen through several strategies:

Data optimization, which calls for “digging in” on performance and cost, and sharing both

Incorporating a pharmacy strategy that includes an evaluation process for making therapy switches

Improving navigation strategy and building a team of nurse and lay personnel, across disease states

Instituting end-of-life strategies that include supportive medicine and social workers

Csik credited the rise of the OCM with driving conversations about improving care that would not otherwise happen. The key now is not just focusing on what payers need, but what patients want as well. “We need to understand what the stakeholders value,” she said.REFERENCE

Caffrey M, Inserro A. Azar announces mandator oncology payment model is coming. 

 website. ajmc. com/newsroom/azar-announces-mandatory-oncology-payment-model- is-coming. Published November 8, 2018. Accessed November 21, 2018.

A recap of the discussion at the Philadelphia meeting of the Institute for Value-Based Medicine®, an initiative of The American Journal of Managed Care®.

Getting the Patient's Viewpoint in the Oncology Quality Equation

Azar Announces Mandatory Oncology Payment Model Is Coming 

A mandatory payment model is coming in oncology care, HHS Secretary Alex Azar said November 8, 2018, during an appearance at a value-based care summit.

Azar said that the administration would “revisit” mandatory models that it had previously scrapped in cardiac care and, in prepared remarks emailed to

 the time had come for “exploring new and improved episode-based models in other areas, including radiation oncology.”

Right now, the Center for Medicare and Medicaid Innovation is working with practices on care transformation through the Oncology Care Model (OCM), but that that 5-year pilot is voluntary.

The Trump administration did not move forward with a mandatory cardiac care model that was developed under the Obama administration and pulled back on bundled payments that were set to be made mandatory in several markets for hip and knee replacements. Those decisions were made by Azar’s predecessor, Tom Price, MD, an orthopedic surgeon who was a known critic of bundled payments.

However, Azar, who previously worked in the pharmaceutical industry, said in prepared remarks to the Patient-Centered Primary Care Collaborative that bundled payments are back, and not just through voluntary programs like the Bundled Payments for Care Improvement initiative, which he said has shown significant savings.

December 2018

From the Editor-in-Chief: Why the Future Never Arrives

Biosimilars Updates

Medical World News: Clinical Updates

Medical World News: Regulatory Updates

Getting the Patient's Viewpoint in the Oncology Quality Equation

Medical World News: Managed Care Updates

Our Contributors/Value-Based Care

Data and Collaboration Are Key for Value-Based Care Success

McAneny Discusses OCM, Community Practices, and Building the Right Rewards

Cancer Today and Cancer Tomorrow: Analysis of US Cancer Claims, 2007-2017

The Future of Cancer Care

Renting Health vs Buying Cures: How New Financing Tools Can Boost Cancer Therapy Development

Increasing Rates of Cancer Screening