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  • The Inevitability of Healthcare IT Interoperability: What We Learned From October 6th

    by Gena Cook, CEO, Navigating Cancer

    Last week, the road ahead for healthcare technology received a flurry of attention, as CMS and the Office of the National Coordinator for Health Information Technology (ONC) released, in one day, an updated version of nearly every document relevant to the healthcare technology sector: Final rules for Stage 3, Final rules for the 2015 EHR certification criteria and the Final version of  the interoperability roadmap from the Office of the National Coordinator for Health Information Technology (ONC). As part of these announcements, CMS included a 60-day public comment period to inform future policy developments, in particular with regard to implementation of the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA). And one week prior, CMS put out a request for public comments on the MACRA provisions for the Merit-based Incentive Payment System (MIPS), Alternative Payment Models (APMs), and physician-focused payment models (PFPMs).

    As our understanding of this whirlwind of information takes shape, we are encouraged to see that the one thing that will truly move the needle on interoperability will now be a requirement in Stage 3: application program interfaces (APIs).

    An API is a set of programming instructions that allows two software programs to communicate with each other. According to the recently-released Stage 3 rules, access to health information through an API is one of the basic actions that a patient should be able to take. For patients, this means the ability to engage in their personal health information via the program of their choosing. For providers, aside from the obvious advantage of no longer being limited to only a fragment of their patient’s actual EHR, this means the opportunity to add-on the modular solutions needed to demonstrate better outcomes and meet the requirements of Alternative Payment Models (APMs) such as Chronic Care Management or the upcoming Oncology Care Model.

    But this is only what it means, in theory. As a modular, EHR-agnostic health IT vendor, with boots on the ground in the struggle for interoperability, we know that the devil is in the details of how interoperability is defined.

    From our experience, what we have learned is that practices are being made to invest considerable time and energy into getting their current EHR vendors to allow interoperability with other vendors. And if they are not careful during the contracting process to ensure that protective language around interoperability be included, practices find themselves subject to information blocking. Some EHR companies have flat out refused to interface with our application, even with signed contracts in place from healthcare professionals. Just as this restricts patients who want to access their electronic health information to the use of suboptimal products today, it impedes practices that want to meet the requirements of new APMs sooner instead of later.

    As described in the Report to Congress on Health Information Blocking, submitted by ONC in April of this year,  economic and market conditions have resulted in business incentives for some entities to exercise control over electronic health information in ways that unreasonably limit its availability and use. And in the Senate HELP Committee hearings on October 1st, ranking member Patty Murray (D-WA) said, “We need to prioritize standards so that increasingly systems developed by different vendors and used by different doctors are actually able to speak to each other. These standards would not only support important research, but they would also cut down the amount of time providers spend on administrative tasks and allow them to focus resources on providing care.”

    Within a short timespan, an individual diagnosed with cancer will interact with multiple care providers. Cancer patients may be seen by their primary care doctor, surgeon, radiation oncologist, medical oncologist and potentially others. We frequently hear from patients who are frustrated by the need to use multiple patient portals or online systems to access their disparate health information – sometimes even within the same health system. While even healthy individuals are challenged to remember multiple logins and product interfaces, cancer patients newly diagnosed and/or in the midst of intensive therapies and subsequent side effects can find it especially difficult to recall and navigate multiple systems of varying designs.

    So, our response to the new regulations that CMS just introduced is this: The API requirement is a great start. Now, specifications around API standardization need to be clearer and tougher. Without this clarity, vendors will be able to create APIs that allow them to check the box but that aren’t actually useful.

    Through the HITECH Act, the federal government has spent more than $30B in EHR meaningful use incentive payments to hospitals and healthcare professionals. But HITECH failed to mandate that EHRs interoperate with other technology solutions. Thus, federal money that was intended to foster an interconnected web of better healthcare delivery instead subsidized the creation of “information silos”: new and formidable hurdles to true patient engagement and care coordination. With the MACRA, congress took a first step by stating that doctors and hospitals that receive EHR bonus payments cannot deliberately block the sharing of information. But these requirements need to hold EHR vendors accountable, not providers.

    We are encouraged by the recent introduction of the bipartisan TRUST IT Act of 2015, also announced on October 6th, which is designed to bring accountability and transparency to health IT vendors insofar as interoperability.

    Now is the time to get the specifications right, and finally realize the promise of health IT.

    To achieve the healthcare transformation that will lead to better outcomes and greater patient satisfaction at economically-sustainable costs, physician practices and hospitals will need more than just the digitization of their clinic workflow that we have now; they will need innovative technologies that truly engage patients and manage high-risk patient populations relative to nationwide benchmarks. API standardization is a landmark opportunity to open up the health IT marketplace and dramatically improve the experience for cancer patients and everyone involved in their care.

    The Landscape of Cancer: Immunotherapy Shining Through

    By: Cory Lewis, Ph.D.

    Immunotherapy is shining through in the crowded space that is oncology, over 6,000 oncology drugs are in development with more than 2,400 different mechanisms of action (MOAs).  Immunotherapies have started to enter the mainstream, with many headlines touting immunotherapy as the Holy Grail of cancer treatment. The immunotherapy market includes more than 75 drugs in development for oncology. The race is now on for the next FDA-approved immunotherapy in cancer as well as expanded indications for the approved immunotherapies, Merck’s Keytruda and Bristol-Myers Squibb’s Opdivo and Yervoy.

    Kantar Health’s newly developed CancerLandscape™ platform identified eight immunotherapy drugs in Phase 3 clinical trials in the U.S., with 13 in Phase 2 and 17 in Phase 1; 41 drugs that target PD-1 alone are in various stages of development, many in preclinical development that may never make it to clinical trials. Given the positive data and recent approvals, companies are trying to expand immunotherapies to other indications. Just looking at Keytruda (Merck & Co.), Opdivo (BMS), atezolizumab (Roche), and Yervoy (BMS) more than 422 trials are currently ongoing. This equates to more than 80,350 patients participating in trials in over 60 different tumor types. Add on top of this, newer target indications that appear almost daily.

    Immunotherapies could completely change treatment paradigms within a tumor. In melanoma, for example, the best option before immunotherapy was interleukin-2, which had an only 6% complete response rate1 with a very large side-effect profile. The level of unmet need was high, and Yervoy was able to reduce the risk of death by 32% in these patients. Recently, Opdivo showed an overall response rate of 32% in advanced melanoma patients and a one-year survival rate of 73%.2,3 In an indication with very few options and dismal outcomes, immunotherapy is allowing patients to live longer.

    Not only are immunotherapies improving clinical outcomes, they also show the potential to affect management of cancer patients in other areas. With immunotherapies moving further up in lines of therapies and quickly becoming the go-to option over chemotherapies, what will happen to the supportive care market? Supportive care drugs used to combat nasty side effects of chemotherapy could see a shrinking market as patients move to immunotherapies with fewer (or at least different) side effects. For example, some supportive care drugs are aimed at neutropenia, but the current approved immunotherapy drugs don’t show a significant amount of neutropenia, and as immunotherapies become more ubiquitous the supportive care market for neutropenia in cancer could shrink.

    • How will immunotherapies change biomarker testing? Specifically, in melanoma, immunotherapy is moving earlier within the treatment paradigm, and treatments are efficacious regardless of BRAF. Will patients still need BRAF testing? If immunotherapy becomes standard of care in first- and second-line in melanoma, where does BRAF testing fit in?
    • What about histology? Immunotherapies in lung cancer seem equally effective in squamous and non-squamous subsets. If immunotherapies become the major treatment in lung cancer does it become necessary to separate the two by histology? Immunotherapy has the ability to not only completely shift a treatment paradigm within a tumor but also to affect other markets and possibly how patients are diagnosed.

    Time will tell how immunotherapies will shape treatment paradigms. However, treatments that powerful have caught the eyes of most companies. According to an in-depth analysis using our CancerLandscape™ platform, of more than 6,000 oncology drugs in development, 77 companies have immunotherapy drugs in their pipelines. Not only is the number of companies with immunotherapy drugs growing but so is the number of clinical trials with existing immunotherapies. Keeping track of who owns which drug and in which indication has become a difficult task with what seems to be a different licensing deal or acquisition every day as companies jockey to have the most promising immuno-oncology drug.

    CTLA4 and PD-1 have been shown to work as targets in several indications. Now we are waiting to see what other indications these targets will work in. The science predicts there may only be a few (those tumors with high tumor burden), but we will have to wait on the data from clinical trials to see if this holds true. Of the new targets on the horizon, what will be next: OX40, LAG-3 or second-generation immuno-oncology agents such as cyclic dinucleotides directed toward the stimulator of interferon genes receptor (STING)? These second-generation compounds provide many more possibilities to investigate and many indications to investigate them in. Agents designed to target natural killer cells and macrophages are in early stages and a new take on immunotherapy drugs in cancer. Will these be able to match the PD-1 data? It will be a fun ride in which some are sure to rise to the top while others may be geared toward niche patient populations. One thing is for sure: immunotherapy will have a long-lasting effect on oncology pipelines.


    1. Atkins MB, Kunkel L, Sznol M, Rosenberg SA. High-dose recombinant interleukin-2 therapy in patients with metastatic melanoma: long-term survival update. Cancer J Sci Am. 2000 Feb; 6 suppl (1):S11-4.

    2. Bristol-Myers Squibb Company. (2014). Opdivo [package insert]. Princeton, NJ: Bristol-Myers Squibb Company.

    3. Bristol-Myers Squibb Company. (2015). Press release June 19. Princeton, NJ: Bristol-Myers Squibb Company.

    Bladder Cancer Treatment IMvigor-ated

    By: Stephanie Hawthorne, Ph.D., Senior Director, Clinical & Scientific Assessment, Kantar Health and Tari Awipi, Ph.D., Associate Consultant, Clinical & Scientific Assessment, Kantar Health

    Approximately 70% to 80% of patients with newly diagnosed bladder cancer will present with superficial or Stage I bladder tumors. Patients with these superficial tumors can often be cured, but those with muscle-invasive or metastatic disease are cured less often and are treated with surgery, irradiation or a combination of modalities that includes systemic therapy. Platinum doublets are widely utilized as first-line treatment in patients with metastatic disease, but minimal options exist for those failing that treatment. No drugs are approved in relapsed/refractory metastatic bladder cancer in the U.S., and the single compound with European approval, Javlor (vinflunine, Pierre Fabre), produced a meager 8.6% response rate and 3.0-month progression-free survival (PFS) in a Phase III trial.1 Thus any serious contender in this setting is a great cause for excitement. With immunotherapy already such a hot topic, atezolizumab (MPDL3280A, Genentech/Roche) is generating considerable enthusiasm.

    Atezolizumab is a human monoclonal IgG1 anti-PD-L1 antibody that inhibits the interaction of the PD-1 receptor with the PD-L1 ligand. In June 2011, a “first-in-human” Phase I (NCT01375842, PCD4989g) trial was initiated to assess atezolizumab in patients with locally advanced or metastatic solid or hematologic malignancies. Preliminary results2,3 from this study in the cohort of patients with advanced bladder cancer were so encouraging that it led to the U.S. Food and Drug Administration (FDA) awarding atezolizumab Breakthrough Therapy status as treatment of relapsed/refractory, PD-L1-positive bladder cancer.

    In the Sunday Proffered Papers session on genitourinary cancers at the 2015 European Cancer Congress,  a packed auditorium eagerly awaited the results of  the Phase II IMvigor 210 trial.4 Data was presented from Cohort 2 of the study, which included 311 patients who were previously treated with platinum-based therapy (Cohort 1 includes platinum-ineligible patients). Atezolizumab was administered at 1200 mg IV every three weeks until loss of clinical benefit. The Ventana PD-L1 (SP142) CDx Assay was used to prospectively stratify participants into three PD-L1-based subgroups based on PD-L1 expression levels in immune cells. IC (tumor-infiltrating immune cell) levels were defined as IC0 for patients with PD-L1 expression in less than 1% of cells (33%, n=103), IC1 for patients with PD-L1 expression in more than 1% but less than 5% of cells (35%, n=108), and IC2/3 for patients with PD-L1 expression in 5% or more of cells (32%, n=100).

    The overall response rate (ORR) was 9% in patients with IC0 expression level, 10% in IC1, 27% in IC2/3, and 15% across all patients. PFS was 2.1 months in all PD-L1 cohorts, although beyond the median there appeared to be a greater PFS in the IC2/3 cohort (PFS at six months was approximately 35% for IC2/3 and 20% for IC0/1). Median duration of response was not reached in any subgroup (range 0+ to 43 months). Median overall survival was 7.9 months across all patient cohorts; median OS was 6.7 months in IC0/1 patients and was not reached in IC2/3 patients. The safety profile of atezolizumab was similar to what has been observed in other tumor types, with 15% of patients experiencing a Grade 3/4 adverse event; treatment discontinuations were infrequent (3%), but dose modifications due to adverse events were common (27%).

    What is most striking about these data is that these are patients who had been heavily treated. Seventy-eight percent had prior systemic regimen treatment for metastatic disease, and 20% had already completed three or more prior lines of therapy. Compared with the 8.6% ORR, 3.0-month PFS, and 6.9-month OS achieved with Javlor in a second-line population, these results are a huge leap.

    With such positive Phase II data, Roche intends to seek regulatory approval, with U.S. and European filings expected to occur in early 2016. Guidance from the company is that they will seek approval in the specific subset of patients with PD-L1-positive disease, although the exact definition of “positivity” intended to be sought is unclear. If they follow their lead from non-small cell lung cancer, the regulatory filing may be limited to patients with IC2/3 PD-L1 expression levels. This would be a wise move, considering that the ORR and PFS were strongest in this patient cohort, although arguably the high unmet need in metastatic bladder cancer could justify the use of atezolizumab in a broad patient population.

    In the U.S., accelerated approval of atezolizumab in this indication is highly likely given the lack of any approved therapies for relapsed patients and with the drug having already received Breakthrough Therapy designation in this indication. An accelerated approval will give atezolizumab a significant first-to-market advantage over its closest competitor in the immuno-oncology space, Keytruda® (pembrolizumab, Merck & Co.). Keytruda is currently being studied in a Phase III trial for relapsed/refractory metastatic bladder cancer, with a trial design that is nearly identical to that of atezolizumab’s Phase III trial in this setting, although Merck’s trial started a few months ahead of Roche’s, lending importance to an accelerated market launch. For a disease that until recently has had so few treatment options, the results from the 2015 European Cancer Congress are truly “IMvigor-ating”.

    1. Bellmunt J, Theodore C, Demkov T, et al. Phase III trial of vinflunine plus best supportive care compared with best supportive care alone after a platinum-containing regimen in patients with advanced transitional cell carcinoma of the urothelial tract. J Clin Oncol. 2009;27(27): 4454-4461.
    2. Powels T, Eder JP, Fine GD, et al. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature. 2014;515: 558-562.
    3. Powles T, Vogelzang NJ, Fine GD, et al. Inhibition of PD-L1 by MPDL3280A and clinical activity in pts with metastatic urothelial bladder cancer. J Clin Oncol. 2014;32(5s): Abstract 5011.
    4. Rosenberg J, et al. Atezolizumab in patients (pts) with locally-advanced or metastatic urothelial carcinoma (mUC): Results from a pivotal multicenter phase II study (IMvigor 210). Vienna, Austria: Proceedings of European Cancer Congress; 2015 Abstract 21LBA.

    Seeing the Forest from the Trees: Atezolizumab in the Rapidly Shifting NSCLC Landscape

    By: Stephanie Hawthorne, Ph.D., Senior Director, Clinical & Scientific Assessment, Kantar Health and Len Kusdra, Ph.D., Analyst, Clinical & Scientific Assessment, Kantar Health

    Without a doubt, PD-1 and PD-L1 inhibitors have taken the oncology field by storm. With its approval in Japan in July 2014 for unresectable melanoma, Opdivo® (nivolumab, Bristol-Myers Squibb/Ono Pharmaceuticals) was the first PD-1 inhibitor to be approved worldwide and represented the culmination of a longstanding quest to harness the body’s inherent immune system to combat cancer. With the proverbial “cat out of the bag,” the approval also sparked a furious race between Opdivo and its closest competitor, Keytruda® (pembrolizumab, Merck), with the U.S. Food and Drug Administration (FDA) granting Keytruda accelerated approval in relapsed unresectable/advanced melanoma (September 2014) and subsequently approving Opdivo in the same setting (December 2014). All eyes turned to non-small cell lung cancer (NSCLC) in March 2015, when Opdivo became first-in-class in this indication with its approval in second-line squamous histology, and Merck quickly followed suit filing for Keytruda in NSCLC (PDUFA date: October 2, 2015). It seemed initially that these two agents would dominate the field of immuno-oncology; however, agents such as atezolizumab (Roche/Genentech), avelumab (Merck Serono/Pfizer), and durvalumab (MEDI4736, MedImmune/AstraZeneca) have entered the fray, and their entry into late-stage development, particularly in NSCLC, has intensified competition with no signs of abating in the near future. A question (among many) now becomes how will all these agents equilibrate in the market and what factors will guide physicians in their treatment paradigms for NSCLC?

    Atezolizumab is Roche/Genentech’s gateway into this hot area. While a slight latecomer, atezolizumab is one of the most advanced immuno-oncology agents, representing a complementary mechanism by being an inhibitor of the PD-L1 ligand. The companies have initiated a broad NSCLC development program for atezolizumab, with three pivotal Phase II trials (FIR, NCT01846416; POPLAR, NCT01903993; and BIRCH, NCT02031458) and one Phase III trial (OAK, NCT02008227) for atezolizumab in second-line NSCLC in an effort to catch up with Opdivo and Keytruda; recently five Phase III trials also were initiated in the first-line setting as well as another Phase III trial in the adjuvant setting. FIR (n=138) and BIRCH (n=667) are single-arm trials of atezolizumab in PD-L1-selected patients in metastatic NSCLC. In both trials, atezolizumab was given at 1200 mg/kg IV every three weeks, and the primary endpoint was objective response rate (ORR). POPLAR (n=287) was a randomized Phase II trial that enrolled all-comers with relapsed metastatic NSCLC, with an accompanied stratification by PD-L1 expression; in this trial, atezolizumab (1200 mg/kg IV every three weeks) was compared with standard-of-care chemotherapy docetaxel (75 mg/m2 IV every three weeks). Roche has consistently guided that these three Phase II trials will form the basis for regulatory applications in the U.S. and Europe.

    Interim results for POPLAR and FIR were first reported at the American Society of Clinical Oncology (ASCO) 2015 annual meeting.1,2 Patients in POPLAR who had higher levels of PD-L1 expression in either the tumor (TC1/2/3) or immune cells (IC1/2/3) showed increased overall survival with atezolizumab compared with docetaxel (median not reached versus 9.1 months (HR 0.63, p=0.024)) and the magnitude of overall survival (OS) benefit was greater for patients who more strongly expressed PD-L1 (immunohistochemistry score (IHC) 2/3, HR 0.56; IHC3, HR 0.46); this survival benefit did not significantly differ among patients with TC or IC IHC0. The FIR trial showed that patients expressing a high level of PD-L1 (TC or IC IHC2/3) exhibited an ORR of 29% for first-line patients, 17% for second-line or later patients without brain metastases, and 23% for second-line or later patients with brain metastases. After POPLAR and FIR reported data at ASCO 2015, the last of the Phase II trials, BIRCH, was highly anticipated. In August 2015, Roche announced that BIRCH had met its primary endpoint and induced tumor shrinkage in patients who expressed PD-L1, and that PD-L1 expression correlated with response; the results were presented Sunday at the 2015 European Cancer Congress in Vienna.3

    The BIRCH trial evaluated atezolizumab in patients with locally advanced or metastatic NSCLC who expressed high levels of PD-L1 on either TC or IC, as determined by the VENTANA SP142 IHC assay. TC2/3 or IC2/3 was equal to or greater than 5% of PD-L1-positive TCs or ICs, while TC3 or IC3 was equal to or greater than 50% TCs or 10% ICs expressing PD-L1. Patients were stratified into three cohorts: Cohort 1 had received no prior chemotherapy (n=142), Cohort 2 had received one prior platinum chemotherapy (n=271), and Cohort 3 had received at least two prior chemotherapies including one platinum (n=254). Patients were treated until progressive disease or until loss of clinical benefit. The ORR in all three patient cohorts correlated with level of PD-L1 expression: ORR for IHC2/3 versus IHC3 was 19% versus 26% in Cohort 1; 17% versus 24% in Cohort 2; and 17% versus 27% in Cohort 3. Median PFS was 5.5 months, 2.8 months and 2.8 in Cohorts 1, 2, and 3 in patients with TC-IC2/3, while a similar trend was seen in patients with TC-IC3 (Cohort 1 5.5 months, Cohort 2 4.1 months, Cohort 3 4.2 months). OS data is not yet mature; however, six-month OS rates in Cohorts 1, 2, and 3 were 82%, 76% and 71%, respectively, in IHC2/3 patients and 79%, 80%, and 75% in Cohorts 1-3 in the IHC3 population. Adverse events seen with atezolizumab were similar to those seen in other studies, with the most common Grade 3/4 adverse events being rash, pneumonitis, elevated liver transaminases and colitis, all which had a frequency less than 2% each.

    Roche has guided that it plans to file for regulatory approval in the U.S. and EU in 2016; in light of the Breakthrough Status granted by the FDA, combined results from FIR, POPLAR, and BIRCH should support an accelerated approval of atezolizumab in patients with PD-L1-positive, relapsed metastatic NSCLC. A question that stands out is how Roche will differentiate atezolizumab from its competitors and how will physicians adopt atezolizumab in their clinical practice. In terms of entry into market, Opdivo is ahead of atezolizumab, allowing Opdivo to establish itself in clinical practice. While cross-trial comparisons should always be made with caution, the survival curves in Opdivo’s CheckMate-017 and CheckMate-057 trials in second-line NSCLC and atezolizumab’s POPLAR trial in second-line NSCLC indicate very similar levels of efficacy between Opdivo and atezolizumab, so similar that the BIRCH trial discussant, Dr. Luiz Paz-Ares, stated that the trials “confirmed each other.” Given the similar level of benefit, it is unlikely atezolizumab will compete with Opdivo based on efficacy alone. Additionally, Keytruda is expected to receive FDA approval in relapsed NSCLC very shortly, thus putting atezolizumab third to market in the U.S.

    One point of differentiation is in patient selection. The data showing increased response in patients with higher PD-L1 supports a regulatory filing in PD-L1-positive patients for atezolizumab, which is also supported by its FDA Breakthrough Therapy designation in this patient type; Opdivo is unlikely to have such a biomarker-restricted label, and whether or not Keytruda’s label will include a biomarker restriction is an area of hot debate. If atezolizumab becomes the first of these drugs to be approved with a PD-L1-positive biomarker limitation in its label, this could prove advantageous. Physicians may shift their preference toward atezolizumab if the efficacy is more pronounced in this patient population or if payers strictly enforce PD-L1 biomarker testing and subsequently choice of PD-1 or PD-L1 inhibitor. The loss of a fraction of patients who are PD-L1-negative if a restricted label is granted may be counterbalanced by the gain of greater market share among patients who are PD-L1-positive than might have been obtained by competing against two other drugs in an all-comers population.

    Many questions remain (largely around implementation of the PD-L1 diagnostic), and physicians will soon find themselves with many arguably similar therapeutic choices for their relapsed NSCLC patients. Until more definitive data becomes available to better guide immuno-oncology treatment decisions, physicians may be left analyzing individual “trees” before the forest that is the clinical paradigm for immuno-oncology products can be fully understood.


    1. Spira AI, Park K, Mazieres J, et al. Efficacy, safety and predictive biomarker results from a randomized phase II study comparing MPDL3280A vs docetaxel in 2L/3L NSCLC (POPLAR). J Clin Oncol. 2015;33(suppl; abstr 8010).
    2. Spigel DR, Chaft JE, Gettinger SN, et al. Clinical activity and safety from a phase II study (FIR) of MPDL3280A (anti-PDL1) in PD-L1–selected patients with non-small cell lung cancer (NSCLC). J Clin Oncol. 2015;33(suppl; abstr 8028).
    3. Besse B, et al. Phase II, single-arm trial (BIRCH) of atezolizumab as first-line or subsequent therapy for locally advanced or metastatic PD-L1-selected non-small cell lung cancer (NSCLC). Vienna, Austria: European Cancer Congress; 2015. Abstract 16LBA.

    CheckMate-025 and METEOR: The Overall Survival Barrier Has Finally Been Broken in RCC

    By: Arnold DuBell, Ph.D., Consultant, Clinical & Scientific Assessment, Kantar Health and Stephanie Hawthorne, Ph.D., Senior Director, Clinical & Scientific Assessment, Kantar Health

    Sutent® (sunitinib, Pfizer) and Votrient® (pazopanib, Novartis) are currently considered the standards of care for first-line therapy in renal cell carcinoma (RCC). However, neither drug (nor any other agents currently approved) has been able to show an overall survival (OS) benefit in clinical trials; they were approved by regulatory agencies based on a significant improvement in progression-free survival (PFS). Since 2005, seven agents have been approved, including Sutent and Votrient, on the basis of PFS alone.

    Moreover, the presence of two established agents with strong utilization in the first-line setting contributes to the need for agents that can be utilized following relapse. Two agents are currently approved for use in this setting – Afinitor® (everolimus, Novartis), based on significant improvements in PFS compared with placebo, and Inlyta® (axitinib, Pfizer), based on significant improvement in PFS compared with Nexavar® (sorafenib, Bayer/Amgen). Given the lack of proven OS benefits for any of these agents, an opportunity exists for an agent that can establish a significant benefit for this endpoint. It is in this framework that  two trials presented in the Presidential Symposium Saturday at the 2015 European Cancer Congress finally show the possibility of improving OS. The trials were CheckMate-025, which evaluated Opdivo® (nivolumab, Bristol-Myers Squibb/Ono), and METEOR, which evaluated Cometriq® (cabozantinib, Exelixis).

    CheckMate-025 was the first of these two studies to be presented.1 This trial compared Opdivo (3 mg/kg every two weeks) to daily oral Afinitor (10 mg) in 821 advanced or metastatic clear-cell RCC patients who had been treated with one or two prior anti-angiogenic therapies. The trial was stopped early by the data-monitoring committee in July 2015 as the statistical boundary for declaring OS superiority of Opdivo had been reached. Opdivo reduced the risk of death by 27% (median OS: 25.0 months versus 19.6 months, HR 0.73, p=0.0018). Most subgroups favored Opdivo, although the arms for elderly patients (75 years or older), patients with favorable MSKCC risk status, or patients who had received two prior therapies (confidence interval overlapped the mark for non-significance)showed no apparent difference ,. Tumor PD-L1 positivity, defined as PD-L1 membrane expression in 1% or more of cells stained using the Dako immunohistochemical kit, was not predictive of activity. The objective response rate was improved (25% versus 5%, OR 5.98, p<0.0001), but the duration of response (12.0 months in both arms) and PFS (4.6 months versus 4.4 months, HR 0.88, p=0.1135) were not improved.

    Opdivo was better tolerated than Afinitor, with fewer treatment-related Grade 3/4 adverse events than Afinitor (19% versus 37%). The more common toxicities of any grade for Opdivo included fatigue (33%), nausea (14%), pruritus (14%), diarrhea (12%), and decreased appetite (12%). The improved efficacy and tolerability were reflected in an improved score in quality of life as measured by the FKSI-DRS questionnaire (p<0.05).

    METEOR was presented next in the session.2 METEOR compared oral daily Cometriq (60 mg) with oral daily Afinitor (10 mg) in 658 advanced clear-cell RCC patients who have progressed on a prior VEGFR tyrosine kinase inhibitor (TKI) within six months of enrollment. Despite that inclusion criterion, there was no limit to the number of prior therapies as 29% of patients on the Cometriq arm received two or more prior VEGFR TKI treatments. Other therapies were also allowed but had been less frequently offered to the enrolled patients.

    METEOR achieved its primary endpoint, which was PFS, with a 3.6-month improvement (HR 0.58, p<0.001). Subgroup analysis suggested that Cometriq improved PFS in most patients, but PFS may not have been significantly improved in those with two or more prior therapies or a poor MSKCC risk status. The response rate was also improved (21% versus 5%, p<0.001). OS was not yet reached but trended to significance with Cometriq (HR 0.67, p=0.005). The medians could not be estimated due to frequent early censoring, and the interim boundary for significance was set at p=0.00019). As the Kaplan-Meier curves were clearly separated from one another and these data are immature, it is expected that a significant OS benefit ultimately will be reached.

    Cometriq had some toxicities but was generally well-tolerated. Grade 3 or 4 adverse events were higher in the Cometriq arm (68% versus 58%) and were reflected in a higher percentage of dose reductions (60% versus 25%). Select Grade 3/4 toxicities of note, compared with Afinitor, included hypertension (15% versus 3%), diarrhea (11% versus 2%) and palmar-plantar erythrodysesthesia (8% versus less than 1%); anemia (5% versus 16%) and hyperglycemia (less than 1% versus 5%) were improved in the Cometriq arm.

    If METEOR does not reach its threshold for statistical significance, the decision for physicians will be easy: Choose Opdivo for its improvement in OS. If the OS benefit in METEOR becomes statistically significant (and the Kaplan-Meier curves strongly suggest that it will do so), then physicians will have a more difficult decision to make. The high excitement level for immuno-oncology agents in general, coupled with its seemingly more favorable tolerability, may lead physicians to opt first for Opdivo. On the other hand, Cometriq does have its own advantages, perhaps most notably the ability to delay progression (by 3.6 months at the median in the METEOR trial).\

    CheckMate 025 METEOR
    Opdivo Afinitor HR Cometriq Afinitor HR
    mOS, mos. 25.0 19.6 0.73 Median not available 0.67
    mPFS, mos. 4.6 4.4 0.88 7.4 3.8 0.58
    Total Grade 3/4 AEs (%) 19 37 68 58

    Making two assumptions – that the METEOR trial ultimately shows a significant OS benefit and that regulatory agencies will approve the two drugs within a few months of each other – these two agents will have a hefty competition for market share in second-line RCC. The toxicity profile for Opdivo may favor its use in many patients, although Cometriq might end up being the agent of choice for select patients, such as those who are older than 75 years of age, where Opdivo appears less effective. In a way, this is a good problem, at least for oncologists and their patients. It’s always better to question which of several good agents to choose from rather than having few options or none at all.


    1. Sharma P, et al. CheckMate 025: a randomized, open-label, phase III study of nivolumab (NIVO) versus everolimus (EVE) in advanced renal cell carcinoma (RCC). Vienna, Austria: European Cancer Congress; 2015. Abstract 3LBA.
    2. Choueiri T, et al. Cabozantinib versus everolimus in patients with advanced renal cell carcinoma: Results of the randomized phase 3 METEOR trial. Vienna, Austria: European Cancer Congress; 2015. Abstract 4LBA.

    Multiple Myeloma and Chronic Lymphocytic Leukemia: Immediate Impact of 2015 ASCO & EHA Presentations on Clinical Practice


    OBR and MDoutlook are pleased to share excerpts from the most recent MDoutlook’s OncoPolls™ from this year’s ASCO and EHA annual meetings. This report highlights certain presentations concerning the treatment of Chronic Lymphocytic Leukemia (CLL) and Multiple Myeloma (MM). This research is based on separate surveys conducted for each hematologic malignancy. The full complimentary report is available through MDoutlook per details below.

    OncoPoll™ Methodology

    • Primary research phase involved global surveys to verified and validated hematologic and medical oncologists with an identified clinical interest in hematologic malignancies utilizing targeting parameters within the proprietary MDoutlook® global cancer treater panel
    • Timing: July 2015. Launched shortly after close of 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, held in Chicago, IL., May 29-June 2, 2015 and the 20th Congress of European Hematology Association (EHA), held in Vienna, Austria, June 11-June 14, 2015
    • Fielding via interactive web-based survey instruments, utilizing proven MDoutlook methodology and proprietary technology
    • Links to discussed abstracts on the ASCO and EHA websites were provided within the survey
    • Responses: 79 global physicians in CLL survey and 75 global physicians in multiple myeloma survey

    Impact of ASCO/EHA Presentations on Ibrutinib Usage in CLL

    Key Conclusions

    • Ibrutinib usage in fludarabine refractory and relapsed CLL will increase from ~1/4 of patients to over 1/3 of patients
      • Usage in fludarabine refractory patients expected to see a 77% increase
      • 58% increase in usage is expected for relapsed CLL
    • In the 1st line setting, ibrutinib usage will also increase, dependent on the patient subtype
    • Overall, the clinical importance of the presentations of the HELIOS clinical trial was rated as 4.25 on a 1-5 scale (data not shown)

    Impact of ASCO/EHA Presentations on Usage of anti-CD20 Antibodies in CLL

    Key Conclusions

    • Based on the presentations at ASCO & EHA (Complement 2 trial), physicians expect to double their usage of obinutuzumab and ofatumumab in CLL
      • Rituximab will remain the dominant choice, with only an absolute loss of ~5% of CLL patients receiving it
    • Overall, the clinical importance of the Complement 2 presentations was rated as 3.54 on a 1-5 scale (data not shown)

    Awareness and Expected Impact of Selected New Agents for CLL

    Key Conclusions

    • 87-88% of physicians have at least some awareness about the bcl-2 inhibitor venetoclax and the PI3K inhibitors duvelisib and TGR-1202
    • Physicians have a very positive outlook for venetoclax, with over 40% expecting this agent to have a large impact on many CLL patients
    • Both new PI3K inhibitors are also positively viewed, albeit slightly less positive than the bcl-2 inhibitor
      • Little to no differences are currently seen between duvelisib and TGR-1202

    Expected Usage of Elotuzumab Today in Relapsed / Refractory Myeloma, if Commercially Available

    Key Conclusions

    • Overall, respondents would use elotuzumab in 58% of their MM patients with refractory disease and 52% of their relapsed MM patients
    • Based on current presentations, ALL respondents would use it in at least some of their MM patients
    • ~40% of physicians would treat most (>60%) of their relapsed / refractory MM patients with elotuzumab

    Expected Impact of Daratumumab for the Treatment of Relapsed Multiple Myeloma

    Key Conclusions

    • Overall impact rated as 5.4 (1 to 7-point scale)
    • 81% of the respondents rate daratumumab as 5 or higher
      • Nobody rates its impact as “Little or none” (1)

    Treatment of Relapsed MM: Kd Expected to Surpass Vd

    Key Conclusions

    • Kd (carfilzomib + dexamethasone) expected to show >50% relative increase in usage in relapsed multiple myeloma, to 38% of patients
    • Expected usage of Vd (bortezomib + dexamethasone) will decrease by ~20% to 1/3 of patients

    Conclusions: Immediate Impact of 2015 ASCO & EHA Presentations on Clinical Practice for CLL & MM


    • Both the HELIOS and Complement 2 clinical trials will impact the CLL treatment landscape
      • Ibrutinib usage is expected to rise by 50% to 110% across all CLL subgroups in the next 6 months
      • Anti-CD20 mAb usage in CLL is slowly shifting from 1st generation rituximab to 2nd / 3rd generation ofatuzumab and obinutuzumab
    • Physicians have very high expectations for the BCL-2 Inhibitor venetoclax in CLL
      • The new PI3K inhibitors duvelisib and TGR-1202 are also positively viewed

    Multiple Myeloma

    • The immune-oncology revolution has come to multiple myeloma with 2 new monoclonal antibodies: the anti-CS1 mAb elotuzumab and the anti-CD38 mAb daratumumab
    • Virtually all oncologists would use elotuzumab in at least some of their relapsed / refractory myeloma patients if it were commercially available today
      • 40% of respondents reported they would use it in 60% or more of their patients
      • Overall, ~50-60% of relapsed / refractory myeloma patients would receive it as treatment
    • Carfilzomib (Kd) is expected to become the preferred proteasome inhibitor over bortezomib (Vd) in the therapy of relapsed MM

    For a more detailed analysis report, please click here to download the full report.

    Submitted by Robert Stephan, Sr. Director Medical Services and Strategy, and Jan Heybroek, President MDoutlook.

    ASCO Attendees Anticipate Increasing Use of Molecular Diagnostics Over Next Decade

    In 2016, the National Institute of Health (NIH) will be introducing the Precision Medicine Initiative, a program designed to better understand the role that individual differences play in health, with a goal of developing better prevention and treatment strategies tailored to the individual.1 The government’s $215 million investment in precision medicine includes $70 million to the National Cancer Institute (NCI) to scale up efforts to identify genomic drivers in cancer and apply that knowledge in the development of more effective approaches to cancer treatment.2 Clearly, the path toward precision medicine and molecular diagnostics is set, and manufacturers, physicians, and payers alike will need to develop their understanding of the challenges and promises they bring.

    For insight into how molecular diagnostics is reshaping oncology treatment, Encuity Research surveyed oncologists immediately after last month’s meeting of the American Society of Clinical Oncology (ASCO). Encuity received responses from more than 100 clinicians engaged in direct patient care, and the results suggest that oncologists fully anticipate the increasing adoption of molecular diagnostics over the next decade.

    Three-quarters of the oncologists surveyed report a high level of familiarity with molecular diagnostics in the cancer marketplace. Thirty-one percent of physicians report that they were exposed to themes concerning molecular diagnostics at ASCO, with the biggest focus on personalized treatment and future use.

    The rise of molecular diagnostics goes against the trend toward treatment pathways over the last decade. For physicians, treatment pathways were appreciated because they offered a certain level of predictability in terms of outcomes. Payers liked them because they helped with budgeting for the next year. Now, however, the use of molecular diagnostics will shift the trend away from grouping patients into certain treatment pathways toward the less structured terrain of personalized medicine.

    Molecular diagnostics requires physicians to look at the patient individually to understand the nuances of the disease—nuances traditional diagnosis methods would not have captured. This may necessitate a change to the treatment paradigm in which treatment pathways tree out into multiple different branches. This is an overarching problem in the market today, and the question faced by physicians is, “Do I trust the new molecular diagnostic test or do I trust the existing standard protocol?”

    More than half of oncologists Encuity surveyed report that they would be likely to use molecular diagnostics for patients who lack other therapy options. But in cases where patients had options, only 24% of oncologists said they’d use the new diagnostic tools. In the same way, physicians are more likely to try the new immunotherapies on patients who have failed to respond to traditional first-line therapies. Doctors report that robust clinical trials with defined outcomes would have the biggest impact on their future use of molecular diagnostics.

    Numerous types of tests fall under the label of molecular diagnostics. Among the most interesting are comprehensive genomic testing, circulating tumor cell tests, and cell-free DNA technology.

    Comprehensive genomic testing uses a single test to provide physicians with a broad view of the targeted treatment options available by detecting all types of alterations, in all the regions where they can occur, for all the genes that are known to be associated with cancer.3

    Cell-free DNA technology and circulating tumor cell technology are genomic tests that do not require a biopsy as in standard genomic testing. Rather than surgically removing tissue from the patient using a needle puncture, cell-free DNA technology and circulating tumor cell technology are diagnostics cased on a blood draw. Because blood sampling can be performed more often, such tests can be used as a diagnostic tool and for monitoring patient progress.

    The vast majority of physicians surveyed are aware of both comprehensive genomic testing (92%) and circulating tumor cell tests (89%), while only 57% of respondents indicated they are aware of cell-free DNA technology. Asked to indicate their level of excitement with regard to the potential impact of these tests on cancer diagnosis and treatment on a scale of 1 (Not At All Excited) to 7 (Extremely Excited), comprehensive genomic tests and cell-free DNA technology received a rating of 5.5, while circulating tumor cell tests received a ranking of 4.7.

    When asked to look out over the next 10 years, oncologists say they expect to see their use of comprehensive genomic testing increase to nearly half their patients, while they anticipate that emerging molecular diagnostic tests will account for one-quarter of their treatment decisions.

    Encuity Research is the marketing research group within Campbell Alliance/inVentiv Health Consulting. For a full version of Encuity’s ASCO Impact Report, please visit http://www.encuity.com/asco.

    By Dave Johnson, Vice President, Encuity Research

    1 The National Institute of Health. Precision Medicine Initiative. Available at http://www.nih.gov/precisionmedicine/. Accessed 6/25/2015.

    2 The White House. FACT SHEET: President Obama’s Precision Medicine Initiative. Available at https://www.whitehouse.gov/the-press-office/2015/01/30/fact-sheet-president-obama-s-precision-medicine-initiative. Accessed 6/25/2015.

    3 Foundation Medicine. Comprehensive Genomic Profiling May Offer More Treatment Options to Patients with Lung Cancer. Available at http://www.foundationmedicine.com/2015/01/comprehensive-genomic-profiling-may-offer-more-treatment-options-to-patients-with-lung-cancer/. Accessed 6/25/2015.

    GI Cancers: Immediate Impact of 2015 ASCO Presentations on Clinical Practice


    OBR and MDoutlook are pleased to share excerpts from the most recent MDoutlook’s OncoPolls™ from ASCO 2015. This report highlights certain presentations concerning the anti-PD-1 / PD-L1 antibody-based Immune Checkpoint Inhibitors and other new agents in Gastrointestinal cancers. This research is based on separate surveys in non-Colorectal Gastrointestinal cancer and Colorectal cancer. The full complimentary report is available through MDoutlook per details below.

    OncoPoll™ Methodology

    • Primary research phase involved global surveys to verified and validated medical oncologists and multi-disciplinary physicians with an identified clinical interest in GI cancers utilizing targeting parameters within the proprietary MDoutlook® global cancer treater panel
    • Timing: June 2015. Launched shortly after close of 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, held in Chicago, IL., May 29-June 2, 2015
    • Fielding via interactive web-based survey instrument, utilizing proven MDoutlook methodology and proprietary technology
    • Links to discussed abstracts on the ASCO website were provided within the survey
    • Responses: 86 global physicians in non-CRC GI Cancer survey and 82 US physicians in CRC survey

    Expected Impact of Immune Checkpoint Blockade Antibodies in Non-CRC GI Cancer

    Key Conclusions

    • Anti-PD-1 / PD-L1 antibodies are mainly expected to have a large impact for small patient groups
      • 27% of the respondents expect large patient collectives to be impacted
      • Only 2% of the respondents expect no impact at all
    • Impact on therapy was estimated marginally higher for Gastric compared to Esophageal and HCC

    Perceived Value of Immune Checkpoint Blockade Antibodies in Non-CRC GI Cancer

    Key Conclusions

    • Overall calculated average of 4.05 (for comparison: NSCLC 4.74 [data: 2015 OncoPoll NSCLC])
    • 15% of physicians perceive the value of these antibodies, at current prices, as being high / very high (for comparison: NSCLC 27% [data: 2015 OncoPoll NSCLC])
    • Two thirds (67%) perceive the value in the medium range (3-5 on a 7-point scale)

    Multi-Factorial Impact of Targeted Agents as a Therapeutic Strategy for BRAF-Mutated mCRC

    Key Conclusions

    • The therapeutic strategy of combining BRAF (+/-MEK) inhibition with EGFR inhibitors is seen to have limited potential for BRAF-mutated mCRC
    • Nearly half of physicians think this approach will have only small impact on a selected few number of these patients
      • A third of respondents think the clinical impact will be larger, but still restricted in the patient subset benefiting from this approach

    Perceived Value of Immune Checkpoint Blockade Antibodies in mCRC

    Key Conclusions

    • Overall calculated average of 4.56
      • Compares with average of 4.74 seen in NSCLC [data: 2015 OncoPoll NSCLC]
    • Over ¼ of physicians (27%) perceive the value of these antibodies, at current prices, as being high / very high

    Expected Impact of PEGH20 on Pancreatic Cancer Treatment Landscape

    Expected Clinical Impact of PEGH20

    Key Conclusions

    • Overall impact rated as 5.56 (1 to 10-point scale)
    • 75% of the respondents expect PEGH20 to make intermediate or high clinical impact

    Regorafenib in Advanced Gastric and Gastric Esophageal Junction Cancer: Expected to be Widely Used

    Expected use of regorafenib in advanced G/GEJ cancer

    Key Conclusions

    • Main usage of regorafenib is expected to be in 3rd and 4th lines of therapy
    • 99% of physicians would use regorafenib in G/GEJ cancers if granted regulatory approval (data not shown)
    • 80% of the respondents expect to use regorafenib in 2 or more lines (data not shown)

    Impact of Abstract# LBA100: Expected Usage of Testing for MMR Deficiency and Treatment with Immune Checkpoint Blockade Antibodies in MMR-Deficient mCRC

    Key Conclusions

    • Physicians expect to test two-thirds of their mCRC patients for mismatch repair (MMR) deficiency over the next 6 months; 45% growth from current levels
      • Almost half of physicians (47%) will test all of their mCRC patients for MMR deficiency (data not shown)
    • Treatment of MMR-deficient mCRC with anti-PD-1/PD-L1 antibodies is expected to nearly double (182%) over the next 6 months
      • 28% of this patient subset is expected to receive this therapeutic approach

    Conclusions: Immediate Impact of 2015 ASCO Presentations on Clinical Practice

    Non-CRC GI Cancers

    • Anti-PD-1/PD-L1 antibodies are expected to have a large impact for selected patients with Gastric, Esophageal and Hepatocellular Cancers
    • At current drug costs, only average value is placed on these agents in GI cancers (lower than what is seen for NSCLC)
    • 75% of the respondents expect the PEGH20 addition to have intermediate or high clinical impact on the treatment of pancreatic cancer
    • Regorafenib will be widely used in advanced G/GEJ cancers upon regulatory approval

    Metastatic Colorectal Cancer

    • The immune checkpoint inhibitors (anti-PD-1/PD-L1) are going to have a very significant impact on the treatment landscape for MMR-deficient mCRC
      • Over a quarter of mCRC patients with this deficiency are expected to receive this treatment almost immediately
      • Most mCRC patients will now be tested for an MMR deficiency
    • At today’s prices, physicians see good value in using the anti-PD-1/PD-L1 antibodies for mCRC
    • Combining BRAF+/-MEK inhibitors with anti-EGFR antibodies is initially seen to have only a limited impact on the treatment of BRAF-mutated CRC

    For a more detailed analysis report, please click here to download the full report.

    Submitted by Robert Stephan, Sr. Director Medical Services and Strategy, and Jan Heybroek, President MDoutlook.

    Is There a Breaking Point for Immunotherapy Costs?

    By: Debbie Warner, Vice President, Oncology Commercial Strategies, Kantar Health

    Value was an overarching theme at ASCO 2015 and has been a topic of ongoing focus, as have been the burgeoning pipeline of immunotherapy agents, with the recently launched PD-1 inhibitors, Opdivo® (nivolumab, Bristol Myers Squibb) and Keytruda® (pembrolizumab, Merck), being the highlights of ASCO 2015. Presenter Leonard Saltz, M.D. of Memorial Sloan Kettering praised the clinical value of an Opdivo + Keytruda combination as being “truly, truly remarkable,” but he added that with the combination costing nearly $300,000 (if continued for 11 months) “these drugs cost too much –unsustainable.” While Dr. Saltz is an unabashed critic of cancer drug prices, $300,000 would give most people pause. Concern about the increasing cost of breakthrough cancer treatment heightens when one considers the number of immunotherapies – like Opdivo and Keytruda – in development for a broad range of solid tumors as well as hematologic malignancies. In fact, at least 33 of the 279 trials studying immune therapies are for combinations with each other and/or in combination with other novel agents. Cost of novel therapy combinations may be the most important factor in limiting these treatments moving forward, and it’s no surprise that discussions of the game-changing nature of immunotherapy are often accompanied by questions of cost sustainability.

    While the easiest way to address the issue of cost may be to dramatically cut prices, development and innovation would no longer flourish. A more realistic approach would be to limit treatment to those patients most likely to respond, as assessed by some objective biomarker. Payers and providers would agree that this makes sense in principle. After all, retrospective analyses of data from clinical trials have shown positive correlations between PD-L1 expression and efficacy. However, researchers are unanimous that there is too much scientific evidence that PD-L1 expression is not an appropriate biomarker for it to be used for patient selection. Further, payers seem unconvinced that biomarkers are the solution. In an April 2015 Kantar Health Oncology Market Access survey, 86 commercial payers expressed tepid enthusiasm about the value of biomarkers.

    Further, only about 30% of payers require submission of a positive biomarker test before approving utilization of drugs with biomarker status specified in their label.

    In the same survey, however, nearly half of payers identified NSCLC and malignant melanoma as the top targets for utilization management. So what are the alternatives?

    Clinical pathways in oncology have garnered tremendous attention over the last few years as a useful tool in improving the value derived from cancer treatment. Though only 20% of payers surveyed identified pathways as the measure most likely to succeed in slowing the growth of treatment costs, 37% indicated that they currently have pathway programs in place. Similarly, 37% of the 150 community oncologists participating in Kantar Health’s Oncology Market Access research indicated that they participate in pathway programs.

    While it is unlikely that payers will absolutely deny coverage of these drugs when they are clinically appropriate, their definition of clinically appropriate is increasingly likely to take into consideration performance status, line of therapy, specific prior therapies and potentially PD-L1 expression.

    Recognizing that they may be fighting an uphill battle in their efforts to strictly manage the utilization of immunotherapies, payers could rely on novel reimbursement approaches that shift reimbursement away from buy-and-bill and toward models that include financial accountability for oncologists. Models such as episode of care reimbursement, accountable care organizations and drug carve-outs can limit payers’ exposure to drug costs while leaving to oncologists’ clinical and fiscal judgment which treatment approach makes the most sense for any particular patient.

    Finally, value-based approaches are being developed, such as ASCO’s Value in Oncology and McKesson’s Value Pathways, powered by NCCN. However, payers are skeptical that simply developing a rating system will have any impact on utilization, especially in the absence of financial risk for oncologists, patients and/or manufacturers.

    That leaves the question of “Where is the breaking point?” That point can only be known after it has passed; presumably no stakeholder wishes to get there. Enter the concept of performance-based pricing. Not a new concept (it is commonly employed in several European countries) it has received significant media attention, most notably calls from Express Scripts to price a drug differentially by indication depending on its efficacy.

    The concept of pricing based on efficacy in an indication or providing rebates on a patient-by-patient basis has merit but will be difficult implement due to an array of challenges, one of which would literally take an act of Congress to close. These challenges include:

    • Arriving at a consensus on the definition of efficacy
    • Siloed budgets between the medical benefit and the pharmacy benefit
    • Ability to capture the necessary data
    • Need for manufacturers to recoup amortized development costs
    • Expected Wall Street reaction to cut in net price
    • Likelihood that payers will “undervalue” even dramatic benefit
    • Government pricing that would at best result in minimal price for all of the drug paid by these programs and at worst severe penalties

    A prospective approach would be ideal but would rely on the ability to limit treatment to patients who will benefit. Unfortunately, science is not there yet for immunotherapy. If and when researchers find an appropriate biomarker, confidence in the reliability of the test will remain a critical issue. Given the potential curative nature of immunotherapy, what level of false negatives will physicians and patients tolerate? This is yet another example of technology outpacing policy.  The question is, when and how will payers and policy-makers catch up?

    Advances in Immunotherapy Stand Out During a Highly Influential ASCO 2015

    Nearly half the oncologists surveyed on the impact of this year’s American Society of Clinical Oncology meeting said they were likely to make changes in patient treatment based on what they learned during the five-day conference.  Forty-nine percent of oncologists said they were very likely or extremely likely to alter treatment strategies, as compared to 24% surveyed last year.

    For the fourth consecutive year, Encuity Research surveyed oncologists immediately after ASCO and received responses from more than 100 clinicians, 90% of whom are engaged in direct patient care. With so much information offered at ASCO that directly impacts treatment decisions, and with four immunotherapy drugs now on the market, it is little wonder that the oncologists found this year’s event to be significantly more valuable than prior years. Sixty-six percent of physicians rated the 2015 conference as very or extremely valuable, 13 points higher than the 53% in 2014.

    For the pharmaceutical and biotech companies developing and commercializing oncology products, the perceptions oncologists take away from ASCO are important, as they help shape prescribing behavior for the coming year. Burrowing down into the details of oncologists’ experience yields other interesting data.

    There was growing, palpable excitement in the meeting rooms and hallways at ASCO around the development of novel immunotherapies and the promise they hold in future treatment. In the survey, oncologists reported plans to expand their use of immunotherapies, particularly in non-small cell lung carcinoma (NSCLC) and melanoma, for which there have been few treatment options. Respondents said that advances in PD-1 and PD-L1 pathways were the most important pieces of new clinical information presented at this year’s conference, followed closely by clinical information on immunotherapies.

    A great many pharmaceutical and biotech companies presented their research at ASCO in both standing-room-only presentations and poster sessions, but Bristol-Myers Squibb stood out from the pack. When asked which companies provided the most valuable information at ASCO, 72% of oncologists cited Bristol-Myers Squibb, more than twice as many as in 2014. Genentech/Roche was ranked second, cited by 60% of oncologists, with Merck seeing a similarly large increase in ratings over last year and ranking third in terms of overall value provided.

    Opdivo (nivolumab) from BMS/Ono was cited by 75% of oncologists (unaided) as the most valuable product-related information at ASCO. The company presented data from three clinical trials, with the highest ranking information from a trial of Opdivo in patients with previously treated advanced or metastatic squamous cell and non-small cell lung carcinoma. Merck’s Keytruda (pembrolizumab) also was ranked as among the most valuable product information. Seventy percent of oncologists rated as valuable Merck’s presentation of data on the combination of Keytruda with low-dose Yervoy (ipilimumab) in the treatment of melanoma and kidney cancer. Oncologists also valued highly valued information presented by Merck on the study of Keytruda plus Yervoy as a second-line therapy for treating non-small cell lung cancer.

    Clinical trial data and perspective presented on Johnson & Johnson and Genmab’s daratumumab monotherapy followed BMS and Merck, with two-thirds of physicians rating the information as very or extremely valuable.

    Another important topic at ASCO this year was molecular diagnostics. In 2016, the National Institutes of Health will be introducing the Precision Medicine Initiative, a program with a goal of developing better prevention and treatment strategies tailored to the individual. Encuity asked ASCO attendees about their views on the emerging topic of molecular diagnostics and found that close to 40% of oncologists report that they are familiar with the Precision Medicine Initiative and three-quarters of respondents report familiarity with the use of molecular diagnostics in cancer treatment. We will delve into the opinions and experiences ASCO attendees have around molecular diagnostics in a future article.

    For a cost-conscious industry research such as this helps measure and refines the effectiveness of communications at critical venues like ASCO. Such research allows companies to understand the impact of the clinical information presented and the relative return on promotional efforts designed to educate physicians’ and influence perceptions, understanding, and intent to prescribe.

    by Dave Johnson, Vice President, Encuity Research.

    For a full version the ASCO Impact Report, please visit http://www.encuity.com/asco