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  • ASCO 2015: PRE-MEETING PRESSCAST

    As preparations for ASCO’s annual meeting heat up, a pre-meeting Presscast highlighted four abstracts of special interest to be presented in greater detail at the meeting in Chicago. All four are based on data from Phase III trials:

    • In the ELOQUENT-2 trial, a new monoclonal antibody — elotuzumab — extended remission when added to standard therapy for relapsed/refractory multiple myeloma
    • A phase 3 double-blind randomized trial showed that daily use of a vitamin B3 pill (nicotinamide) reduces incidence of new non-melanoma skin cancers (basal cell and squamous cell cancers), as well as pre-cancerous actinic keratoses in people at high risk for skin cancer
    • Data from two Phase III Children’s Oncology Group Studies show that a specific genetic abnormality enables more intensive therapy to be given to children with Wilms Tumor, thereby improving outcomes in this high-risk group
    • Results from STAMPEDE show that docetaxel — but not zoledronic acid — extended overall survival when given with hormone therapy to men with newly diagnosed, metastatic, hormone-naive prostate cancer

    “Trials like these are engines of progress for people with cancer of all ages. In just four studies, we see the potential to spare thousands of people the stress and complications of a new cancer diagnosis, and to extend the lives of children and adults facing cancer in its most daunting forms. At ASCO’s meeting in Chicago, we’ll continue to see the transformative power of investments in cancer research and care,” stated ASCO President Peter Paul Yu, MD, FACP, FASCO, in an official press release.

    Elotuzumab in Multiple Myeloma
    Interim results of a Phase III trial show that adding the monoclonal antibody elotuzumab to standard therapy with lenalidomide/dexamethasone reduced the risk of cancer progression and death by 30% in patients with relapsed/refractory multiple myeloma.

    “This therapy combines the precision of a targeted, immune-based therapy with traditional myeloma therapy. The results are very encouraging, giving renewed hope to patients who have relapsed,” stated ASCO President-Elect Julie M. Vose, MD, who was not involved in this trial.

    “Elotuzumab acts on the tumor cell and enhances the activity of natural killer cells, providing a sort of ‘double whammy’,” said lead author Sagar Lonial, MD, Winship Cancer Institute of Emory University School of Medicine, Atlanta, GA. “We are excited about the progression-free survival results attributable to this novel first-in-class antibody.”

    This is the largest study of a targeted monoclonal antibody in multiple myeloma and the first Phase III study to show the benefit of this approach in multiple myeloma. The study randomized 646 patients with relapsed/refractory multiple myeloma to standard therapy with lenalidomide/dexamethasone or standard therapy plus elotuzumab. At a median follow-up of 24 months, progression-free survival (PFS) was 41% in the triple therapy arm versus 27% in the standard therapy arm (P=.0004).

    “It is striking that these curves remain separated at 2 years, which speaks to the power of an immune approach as part of treatment of multiple myeloma,” Dr. Lonial commented.

    Importantly, patients at high risk due to genetic abnormalities — del(19p) and t(4;14) — had similar benefit from elotuzumab as in the overall study. These patients typically have less benefit from conventional therapies, Dr. Lonial said.

    Overall elotuzumab was well tolerated with no significant increases in adverse events. About 10% of patients experienced a mild infusion reaction with the first few doses of the monoclonal antibody. Elotuzumab has been granted a Breakthrough Designation by the U.S. FDA.

    Vitamin B3 Supplement (Nicotinamide) and Skin Cancer
    An oral form of vitamin B3 (nicotinamide) taken twice daily for 12 months reduced the rate of new skin cancers by 23% compared to placebo in people at high risk for these cancers. This simple, inexpensive pill is safe, affordable, and available over the counter, making it widely available for people at risk.

    “When we stopped treatment, there was no difference between the two arms, suggesting that continuous treatment is needed. I should emphasize that these results pertain to high-risk patients who have had other skin cancers, not the general public,” said lead author Diona Damian, MBBS, PhD, Dermatology University of Sydney, Australia.

    “The pill does not take the place of sunscreen use and regular skin check-ups for people at high risk,” she emphasized.

    The study included 386 patients who had at least two non-melanoma skin cancers over the past 5 years and were therefore deemed high risk. Patients were randomized to daily nicotinamide or placebo for 12 months. Dr. Damian said the patient mix reflected those seen in a typical skin cancer clinic. Average age was 66 years and two thirds were men, many with ongoing chronic comorbidities.

    Nicotinamide reduced the rates of new basal cell cancer and squamous cell cancer diagnoses by 23% compared with placebo. Nicotinamide reduced the rates of actinic keratoses (pre-cancers) by 11% at 3 months and by 20% at 9 months of treatment compared with placebo.

    This preventive treatment has no side effects, Dr. Damian said.

    High-Risk Wilms Tumor
    Intensifying therapy for children with Wilms Tumor improves outcome in patients with a chromosomal abnormality associated with poorer prognosis, according to results of two Phase III trials conducted by the Children’s Oncology Group.

    Previous studies of patients with the genetic abnormality treated with conventional regimens showed 4-year relapse-free survival rates of 74.9% for stage I/II disease and 65.9% for stage III/IV disease. Intensified, or augmented therapy, increased the rates to 83.9% and 91.5%, respectively.

    “Augmentation of therapy for favorable histology Wilms Tumor with LOH improves outcomes, particularly for stage III/IV disease. We are encouraged that augmentation can overcome a known adverse biomarker,” said lead author David B. Dix, MD, British Columbia Children’s Hospital, Vancouver, Canada.

    The AREN0533 and ARENO532 studies evaluated whether augmenting therapy would improve event-free survival for patients with favorable Wilms histology and the genetic abnormality (tumor-specific loss of heterozygosity [LOH] of chromosomes 1p and 16q). Augmentation strategies were as follows:

  • Stage I/II patients received doxorubicin in addition to vincristine/dactinomycin, and
  • Stage III/IV patients received all three drugs alternating with cyclophosphamide/etoposide and radiotherapy
  • At a median follow-up of 3.6 years, of a total of 1134 patients, 35 stage I/II patients and 52 stage III/IV patients had combined LOH 1p and 16q; these patients formed the basis of the analysis. Grade 3 or higher hematologic toxicity was the most common adverse event observed with the augmented regimen given to stage III/IV patients, occurring in 60%. The analysis did not establish superiority of either augmented regimen.

    LOH 1p, 16q testing is considered the standard of care at the Children’s Oncology Group Biopathology Center and several other centers, Dr. Dix noted.

    Docetaxel for Hormone-Naive Advanced Prostate Cancer
    The STAMPEDE trial found that the addition of docetaxel to standard hormone therapy improved overall survival (OS) by a median of 10 months in men with newly diagnosed advanced prostate cancer who were previously naive to hormone therapy; however, the addition of zoledronic acid to standard therapy had no effect on survival in this group of men and the combination of docetaxel plus zoledronic acid was not superior to docetaxel alone.

    “Docetaxel chemotherapy should be routine in men with newly diagnosed metastatic prostate cancer about to start hormones for the first time. There is some uncertainty regarding the survival benefit in men with non-metastatic prostate cancer, but docetaxel should be offered upfront to these men to prolong failure free survival,” said lead author Nicholas David James, MD, PhD, University of Warwick in Coventry, U.K. ” It’s clear that zoledronic acid does not benefit these patients and should not be offered as upfront treatment for advanced prostate cancer.”

    STAMPEDE is the largest randomized clinical trial conducted to date of treatment for prostate cancer, including more than 6500 men enrolled since 2005. The innovative, ongoing, multi-arm study has an adaptive trial design, modifying the standard of care (SOC) control, arm as new patients are continuously enrolled. Ineffective treatments are dropped and new arms are added to assess the efficacy of newer treatments. The control, or standard of care (SOC) arm, has evolved over time.

    Results to be presented at ASCO 2015 focus on 2962 hormone-naive men assigned to one of 4 of STAMPEDE’S 9 different treatment arms: SOC, SOC with docetaxel for 6 cycles, SOC with zoledronic acid for 2 years, and SOC with both docetaxel and zoledronic acid.

    By Don Sharpe

    Kantar Health Offers a Preview of the Pivotal Abstracts at ASCO 2015

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

    The annual meeting of the American Society of Clinical Oncology (ASCO) is nearing, and Kantar Health has identified several pivotal abstracts that will be presented. The 2015 ASCO annual meeting promises to be packed with the latest data and trends from the world of oncology, and the meeting has the potential to alter treatment practices in several tumor types. The following is a brief discussion of three abstracts that are likely to generate the most discussion and have the highest impact. For a full discussion of all 10 of our top abstracts, please see the associated article in the May issue of OBR Green.

    Imbruvica plus R-Treanda in relapsed/refractory chronic lymphocytic leukemia (CLL) – HELIOS trial

    Pharmacyclics and Janssen have been aggressively developing Imbruvica® (ibrutinib) across a number of settings in B-cell malignancies, including CLL and non-Hodgkin’s lymphoma (NHL). This strategy has paid off with Imbruvica’s approval as monotherapy in CLL patients with del17P, in previously treated CLL patients, in Waldenström’s macroglobulinemia, and in previously treated mantle cell lymphoma (accelerated approval). In CLL, the company is looking beyond its approval as monotherapy and hopes that combining Imbruvica with the standard-of-care chemotherapy backbone in second-line ― Rituxan® (rituximab, Genentech/Roche) and Treanda® (bendamustine, Teva/Mundipharma) ― will yield a stronger effect compared with Rituxan-Treanda in the relapsed/refractory setting.

    In March 2015, Janssen announced that the independent data monitoring committee (IDMC) unanimously recommended unblinding the HELIOS trial (NCT01611090), an international Phase III, placebo-controlled trial comparing the efficacy of Imbruvica in combination with R-Treanda versus placebo plus R-Treanda in relapsed/refractory CLL and small lymphocytic lymphoma (SLL).1 The IDMC’s recommendation came as a result of the study having met its primary endpoint, demonstrating a significant improvement in progression-free survival (PFS) with Imbruvica in combination with R-Treanda.

    The HELIOS trial is a step toward expanding Imbruvica into earlier lines of therapy, since R-Treanda is a commonly used chemotherapy regimen in first- and second-line CLL. In the Phase III RESONATE trial that compared Imbruvica with Arzerra® (ofatumumab, Novartis) in relapsed/refractory CLL, the hazard ratio for PFS was 0.215 and for overall survival (OS) was 0.434.2 It remains to be seen whether the addition of Imbruvica to R-Treanda can elicit this same magnitude of benefit, or whether the level of improvement will be more muted when used in combination with an active regimen. In that respect, the PFS curves will be an important metric to examine at ASCO.

    The safety profile in the HELIOS trial also will be key during the presentation, in particular the incidence of neutropenia. Treanda was associated with Grade 3/4 neutropenia in 43% of patients in its Phase III trial in relapsed/refractory CLL, and neutropenia was also the most common Grade 3/4 adverse event that occurred in the Imbruvica arm of RESONATE (16% of patients). Some myelosuppression may be inherent to leukemia, but it will be important to confirm that the combination of drugs won’t exacerbate this toxicity, particularly in a disease that is associated with a more elderly population.

    Abstract LBA7005, Saturday May 30, 2:27 PM

    Opdivo plus Yervoy in first-line metastatic melanoma – CheckMate-067 trial

    Historically, prognosis for metastatic melanoma has been poor, with median OS of less than a year and treatment usually involving toxic and mostly ineffective agents. This changed with the approval of Yervoy® (ipilimumab, Bristol-Myers Squibb) in 2011, which improved OS and provided evidence of potentially curative effects, measured as a 20% five-year survival rate.3

    Yervoy is not without shortcomings, primarily its association with severe immune-related adverse events (irAEs), liver toxicity and gastrointestinal side effects occurring in over a quarter of patients, requiring close monitoring and supportive care with steroid and immunosuppressant treatment. Additionally, while Yervoy induces long-term survival in a fraction of patients, the majority does not enjoy such a benefit, leaving room for agents that can induce a higher level and longer duration of response and survival.

    Since Yervoy’s approval, the development of checkpoint inhibitors has proceeded rapidly, particularly with PD-1/-L1 inhibitors. Keytruda® (pembrolizumab, Merck & Co) and Opdivo® (nivolumab, Bristol-Myers Squibb/Ono Pharmaceuticals) are the frontrunners and are now FDA approved for the treatment of unresectable/metastatic melanoma following Yervoy and a BRAF inhibitor (in patients with a BRAF mutation).

    Keytruda has recently shown superiority to Yervoy in a head-to-head comparison of the two monotherapies in metastatic melanoma.4 BMS is taking an alternative approach, with hopes that a combined approach ― Yervoy plus Opdivo ― will act in synergy to further improve outcomes over each agent alone. Based on a high response rate in early clinical trials, the company initiated the Phase III CheckMate-067 trial (NCT01844505) to evaluate the impact of the combination of Yervoy and Opdivo on PFS and OS versus either single agent. On May 31, initial data from CheckMate-067 will be presented at ASCO.

    Positive results from CheckMate-067 will solidify the combination of Yervoy plus Opdivo as the standard of care replacing checkpoint inhibitor monotherapy, thus staving off competition from Merck’s Keytruda. In addition, efficacy of Yervoy and Opdivo in both BRAF-mutant and wildtype patients may lead to the combination replacing tyrosine kinase inhibitors for BRAF-mutant patients if the response rates and long-term survival are sufficiently convincing.

    Early clinical trials reported a high response rate (40%) with the combination.5 Will that hold up in CheckMate-067, and will it translate into PFS and OS benefits? In the CheckMate-066 trial, Opdivo monotherapy produced a one-year OS rate of 72.9% (too soon to estimate five-year OS), and in Yervoy’s pivotal first-line trial one-year OS was 47.3%.3 Where will the curves fall for the combination? Unfortunately, it’s too early to get a feel for long-term survival (the trial has been ongoing for only two years), but even the early timepoints of the curve will be informative to appreciate how much the curves are diverging.

    Secondary endpoints to pay attention to include safety and biomarker analyses. Given the current debate on PD-L1 marker status it will be interesting to assess whether PD-L1 expression on either the tumor or on tumor-infiltrating lymphocytes will meaningfully affect benefit, and if so how PD-L1 positivity will be measured. Additionally, Yervoy and Opdivo have both distinct and overlapping toxicity profiles, so it will be important to determine whether the combination will be manageable and the benefit outweighs the risk.

    Abstract LBA1, Sunday, May 31, 1:35 PM

    Ibrance plus Faslodex in pretreated HR+ metastatic breast cancer – PALOMA-3 trial

    Endocrine therapy is the mainstay of management for patients with metastatic hormone receptor positive (HR+) breast cancer. Long-term hormone therapy is preferred before resorting to more toxic chemotherapy, and while endocrine therapy is very effective in extending disease control in these patients, most will eventually progress. Ibrance is a dual CDK4/6 inhibitor that has been shown to inhibit components of the pathway that drives cell division, leading to cell cycle arrest and subsequent cell death. Results from the randomized Phase II PALOMA-1 trial (NCT00721409) showed that the combination of Ibrance with letrozole significantly improved PFS compared with letrozole and placebo in the first-line setting,6 which led to Ibrance’s accelerated approval in February 2015. At ASCO, we will hear results from the Phase III PALOMA-3 trial (NCT01942135), which compares Ibrance in combination with Faslodex® (fulvestrant, AstraZeneca) versus Faslodex alone for the treatment of patients with HR+, HER2- metastatic breast cancer patients who have progressed on prior endocrine therapy.

    The trial was stopped early because it had met its primary endpoint of improvement in PFS as assessed by the IDMC.7 PALOMA-3 is in a second-line setting, so the number of months’ benefit may be muted in comparison to PALOMA-1, but will the relative magnitude of benefit (a 51% reduction in the risk of progression or death in PALOMA-16) be retained? Another aspect of the data that will be interesting to note is whether Ibrance will be equally active in an HR+ population as it is in the ER+ population that was enrolled in PALOMA-1.

    The use of these agents in combination with hormone therapy raises the risk of increased side effects in a treatment setting that has long been sheltered from significant toxicity. Hematological adverse events were seen in a significant portion of patients in the PALOMA-1 trial. Clearly, this is a parameter that will be closely examined during the PALOMA-3 presentation and will be weighed against the efficacy benefit. If the efficacy benefit in PALOMA-3 is not as large as seen in the first-line setting, the balance between efficacy and toxicity will be more important.

    Building on its recent accelerated approval in front-line in the U.S., PALOMA-3 results will broaden Ibrance’s utilization opportunities, giving physicians flexibility to combine with letrozole or Faslodex and data to support use in the first- or second-line settings. In addition, PALOMA-3 will support regulatory filings outside the U.S., making Ibrance the second targeted agent to be approved in combination with hormone therapy in metastatic HR+/HER2- breast cancer.

    Abstract LBA502, Monday, June 1, 8:24 AM


    References:
    1) Independent Data Monitoring Committee Unanimously Recommends Unblinding of IMBRUVICA® (ibrutinib) Phase III Combination HELIOS Trial Based on Interim Analysis Showing Significant Improvement in Progression-Free Survival in Patients with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma [press release]. Sunnyvale, CA: Pharmacyclics; March 16, 2015.
    2) Byrd et al., N Engl J Med. 2014; 371: 213-223.
    3) Maio et al., J Clin Oncol. 2015;33(10):1191-1196.
    4) Ribas et al., N Engl J Med. 2015;372:320-330.
    5) Wolchok et al., N Engl J Med. 2013;269(2:122-133.
    6) Finn et al., Lancet Oncol. 2015;16(1:25-35.
    7) Pfizer Announces PALOMA-3 Trial For IBRANCE® (Palbociclib) Stopped Early Due To Efficacy Seen In Patients With HR+, HER2- Metastatic Breast Cancer Whose Disease Has Progressed Following Endocrine Therapy [press release]. New York, NY : Pfizer ; April 15, 2015.

    The Battle for Dominance of the Advanced Melanoma Market Continues

    By: Arnold DuBell, Ph.D., M.B.A, Consultant, Clinical and Scientific Assessment, Kantar Health and Greg Wolfe, Ph.D., Senior Consultant, Clinical and Scientific Assessment, Kantar Health

    Recent progress in the development of novel therapeutic agents to combat melanoma has been tremendous. Immune checkpoint inhibition and targeted inhibition of BRAF and MEK are two therapeutic approaches that have significantly improved survival for patients with advanced melanoma. Since 2011, the Food and Drug Administration (FDA) has approved three checkpoint inhibitors: starting with the CTLA4 inhibitor Yervoy® (ipilimumab, Bristol-Myers Squibb), with subsequent approvals of PD-1 inhibitors Keytruda® (pembrolizumab, Merck & Co.) and Opdivo® (nivolumab, Ono/Bristol-Myers Squibb).

    Immune checkpoints play critical roles in balancing co-stimulatory and co-inhibitory signals that regulate human self-tolerance and control the amplitude and duration of T-cell responses. PD-1 is a key immune checkpoint receptor expressed on activated T-cells. Binding of PD-1 to its ligand (PD-L1) results in suppression of the immune response, and tumor cells can manipulate this critical pathway to elude attack by tumor-infiltrating T-cells.

    Opdivo holds the title of the first PD-1 inhibitor to gain global regulatory approval when it was approved in Japan in July 2014 for melanoma. In September 2014, Keytruda became the first PD-1 inhibitor to gain approval in the U.S. when the FDA awarded Keytruda accelerated approval for treatment of patients with unresectable or metastatic melanoma and disease progression following Yervoy and, if BRAF V600 mutation positive, a BRAF inhibitor. However, the race to the U.S. market was tight as Opdivo received accelerated approval from the FDA in December 2014 for a similar indication. Although both Keytruda and Opdivo were approved for previously treated melanoma, the National Comprehensive Cancer Network (NCCN) was sufficiently convinced by these agents’ activity in pretreated patients that the latest guidelines (v3.2015) recommend consideration of use of both Opdivo and Keytruda instead of Yervoy in the first-line setting. With the battle now shifting to treatment-naïve advanced melanoma, these agents need to prove their superiority to Yervoy, which has ruled as the only approved checkpoint inhibitor in the U.S. since 2011.

    Results from the Phase III KEYNOTE-006 trial (NCT01866319) were presented Sunday at the AACR (American Association of Cancer Research) Annual Meeting in Philadelphia.1 Merck initiated this pivotal, three-arm trial in August 2013 to evaluate the safety and efficacy of two dosing schedules of Keytruda compared to Yervoy for the treatment of Yervoy-naïve patients with unresectable or metastatic melanoma. In this study 834 unresectable, Stage III/IV patients were randomized (1:1:1) to receive Keytruda (10 mg IV) either once every two weeks (Q2W) or once every three weeks (Q3W) for up to two years or Yervoy (3 mg/kg IV) once Q3W for a total of four doses (the approved Yervoy dose regimen). Eligible patients may have received one or fewer prior therapy excluding anti-CTLA4, PD-1 and PD-L1 agents; one-third of enrolled patients had received prior therapy, typically chemotherapy or a BRAF inhibitor (one-third of enrolled patients had BRAF mutations). Progression-free survival (PFS) and overall survival (OS) were co-primary endpoints.

    Keytruda was superior to Yervoy in all key study endpoints. Median PFS was 5.5 months for Keytruda (Q2W), 4.1 months for Keytruda (Q3W), and 2.8 months for Yervoy; PFS rates at six months were 47.3% for Keytruda (Q2W) (HR= 0.58; p<0.00001), 46.4% for Keytruda (Q3W) (0.58; p=0.00001), and 26.5% for Yervoy. Median OS data was immature for all study arms, while the OS rates at 12 months were 74.1% for Keytruda (Q2W) (HR= 0.63; p<0.00052), 68.4% for Keytruda (Q3W) (0.69; p=0.00358), and 58.2% for Yervoy. Overall response rates (ORR) were 33.7% for Keytruda (Q2W) and 32.9% for Keytruda (Q3W), versus 11.9% for Yervoy. Keytruda also demonstrated a superior safety profile compared with Yervoy. Grade 3 to 5 adverse events attributable to study drugs were reported in 13.2% (Keytruda Q2W), 10.1% (Keytruda Q3W), and 19.9% (Yervoy) of patients with events similar to what is characteristic of the class but with individual adverse events occurring rarely; rates of treatment discontinuation due to treatment-related adverse events were 4.0%, 6.9%, and 9.4%, respectively. As OS results at the second interim analysis crossed the prespecified efficacy boundary, the KEYNOTE-006 trial was halted early and results were unblinded; however, the study is ongoing for safety and survival follow-up until the final analysis.

    Compared with patients randomized to Yervoy, patients randomized to Keytruda experienced a 1.8-fold improvement in the six-month PFS rate, a reduction in risk of death of 31% to 37%, and a 2.8-fold increase in ORR. With such strongly positive results from KEYNOTE-006 in hand, Merck will move toward regulatory filing of Keytruda in the first-line setting as quickly as possible. As Keytruda demonstrated significant improvement in both PFS and OS compared with Yervoy, it is evident that Yervoy’s dominance as front-line standard of care for BRAF-wildtype patients will soon fade away as PD-1 checkpoint inhibitors assume this role.

    The question remains as to which PD-1 inhibitor will win the battle for the front-line setting. Although the results from KEYNOTE-006 are outstanding, one must not forget that in June 2014 Bristol-Myers Squibb announced preliminary results of their Phase III CheckMate-066 trial (NCT01721772) that evaluated Opdivo versus dacarbazine as first-line therapy in 418 patients with unresectable Stage III or Stage IV melanoma. CheckMate-066 was prematurely terminated because the independent data-monitoring committee confirmed a significant OS benefit was achieved (BMS press release, June 25, 2014). Median OS was not reached for the Opdivo arm and was 10.8 months for the dacarbazine arm (p=<0.001). One-year survival was 73% for Opdivo-treated patients versus 42% for dacarbazine (p<0.0001); median PFS was 5.1 months for the Opdivo arm versus 2.2 months for dacarbazine; and objective response rates were 40.0% versus 13.9% for Opdivo and dacarbazine, respectively.2 Drug-related Grade 3/4 adverse events occurred in 12% of patients treated with Opdivo and 18% of patients treated with dacarbazine, with only 2% and 3% of patients, respectively, discontinuing due to adverse event. If one indulges in a cross-trial comparison (with all of the usual caveats) with regard to PFS, OS and ORR, Keytruda and Opdivo appear to have quite similar efficacies and safety profiles as front-line agents for advanced/metastatic melanoma. With the activity of Keytruda and Opdivo appearing so similar, how will physicians choose between two highly active agents? Although Opdivo was the first to report results of the first-line randomized trial, it was in comparison with a now-defunct standard of care (dacarbazine). Keytruda may be at an advantage in having shown clear superiority against the current standard of care, Yervoy. That could propel physicians to preferentially utilize Keytruda. However, it should not be overlooked that the dose of Keytruda utilized in the KEYNOTE-006 trial (10 mg/kg Q2W or Q3W) is significantly higher than the dose at which it is currently approved (and priced) in the relapsed/refractory setting (2 mg/kg Q2W). At the currently approved dose, Keytruda costs $12,500 per month; at the dose tested in the KEYNOTE-006 trial, the monthly price for Keytruda would presumably be in excess of $60,000 per month. Clearly this is not sustainable, so cost of therapy could become a major decision factor when choosing between Keytruda and Opdivo (at the dose tested in CheckMate-066 and -067, the cost per month is $12,500), unless the pricing of the higher dose of Keytruda is creatively managed.

    Bristol-Myers Squibb is not far behind with its own trial comparing Opdivo with Yervoy. The company is conducting the Phase III CheckMate-067 trial (NCT01844505) to determine whether Opdivo alone or Opdivo in combination with Yervoy will extend survival compared with Yervoy alone in patients with previously untreated metastatic melanoma. OS and PFS are co-primary endpoints. Given the results of KEYNOTE-006, one would expect that Opdivo also will be able to best Yervoy when comparing the two monotherapies. CheckMate-067 will confirm these expectations, but perhaps more importantly will inform how efficacy of the combination of inhibition of PD-1 and CTLA4 checkpoint pathways compares to a PD-1 inhibitor alone. What level of gain in survival can be expected with this dual-blockade? Will toxicity of the combined agents be insurmountable?

    Between the CheckMate-066 results first reported at the Society of Melanoma Research in November 2014, the KEYNOTE-006 results reported at AACR in April 2015, and looking ahead to the widely anticipated CheckMate-067 trial readout, a heated battle is playing out among the checkpoint inhibitors in advanced melanoma. With both PD-1 inhibitors showing one-year overall survival in excess of 70%, compared with less than 40% one-year survival historically,3 this battle is turning into a win-win for patients and physicians.

    References:

    1. Ribas A, Schachter J, Long GV et al. Phase III study of pembrolizumab (MK-3475) versus ipilimumab in patients with ipilimumab-naive advanced melanoma. AACT Abstract CT101, 2015.

    2. Robert C, Long GV, Brady B et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Eng J Med. 2014;372:320-330.

    3. Kantar Health, CancerMPact® Patient Metrics U.S., accessed April 19, 2015.

    VEGF TKI Adjuvant Therapy in RCC Does Not ASSURE Improved Clinical Outcomes

    Surgical resection is the primary treatment for patients with early-stage renal cell carcinoma (RCC) and can potentially be curative in up to 70% of cases.1 In many solid tumors, patients at high risk of recurrence are often treated with adjuvant (postsurgical) systemic therapy, with the idea being to eradicate any microscopic residual disease and thus decrease the likelihood of developing a local or metastatic recurrence. While adjuvant therapy is standard of care in many solid tumors, no adjuvant therapy has proven to increase disease-free survival in RCC; furthermore, cytokine therapies that have been studied in the adjuvant setting, such as interleukin and interferon-α, carry high levels of toxicity. As such, adjuvant therapy is rarely administered (approximately 26% of Stage III patients are administered adjuvant therapy in the U.S.2).

    Nexavar® (sorafenib, Onyx / Amgen) and Sutent® (sunitinib, Pfizer) changed the treatment paradigm for advanced/metastatic RCC when they were first launched nearly a decade ago. Their widespread use in advanced RCC has also prompted debate whether they would be equally active in the adjuvant setting. While use of adjuvant therapy is minimal in RCC, among those patients who do receive an adjuvant regimen, Sutent and Nexavar are used off-label in approximately 45% of patients.2 Both agents have demonstrated increased efficacy in advanced/metastatic RCC and have good safety profiles, even for extended periods of administration, making them good candidates for adjuvant therapy. ASSURE (adjuvant sorafenib or sunitinib in unfavorable renal cell carcinoma; Eastern Cooperative Oncology Group 2805) is a Phase III trial investigating the clinical benefit and tolerability of these therapies in the adjuvant setting. ASSURE is a randomized, double-blind, multicenter trial that enrolled 1,943 patients with resected, intermediate and very high risk (as scored by UISS risk criteria1), clear cell and non-clear cell RCC who had no prior systemic therapy. Patients were randomized to one year treatment with Nexavar (400 mg twice daily, administered continuously for nine cycles), Sutent (50 mg once daily, administered for four weeks of a six-week cycle for nine cycles), or placebo. Notably, drug dosage was reduced to 400 mg Nexavar and 35 mg Sutent both given once daily as a result of adverse events and patient intolerance (see further detail below). Moreover, the sample size was increased from 1,332 patients to 1,943 patients to compensate for the dosage revision. Disease-free survival (DFS) was used as the primary endpoint, and secondary endpoints were overall survival (OS) and tolerability. Additionally, examination of angiogenic markers in tissue, blood, and urine was performed to determine their significance in predicting therapeutic benefit.

    Initial results of ASSURE, reported at the 2015 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, demonstrated that Nexavar and Sutent do not improve clinical efficacy in the adjuvant setting.3 Median DFS was 5.8 years in the Nexavar and Sutent treatment arms and 6.0 years in the placebo arm (Nexavar vs. placebo HR = 0.97, p = 0.74; Sutent vs. placebo HR = 1.00, p = 0.96). Moreover, five-year DFS rates were 52.8% in the Nexavar arm (HR = 0.98), 53.8% in the Sutent arm (HR = 1.01), and 55.8% in the placebo arm. Five-year OS rates were 80.7% in the Nexavar arm (HR = 0.93), 76.9% in the Sutent arm (HR = 1.10), and 78.7% in the placebo arm.

    Not only was efficacy not improved with the use of Sutent or Nexavar in the adjuvant setting, these regimens added significant toxicity. Both agents were associated with an increased incidence of hypertension, a class effect for VEGF pathway inhibitors (16% Nexavar, 16% Sutent, 4% placebo). Nexavar was also associated with increased incidence of hand-foot syndrome (15% vs. <1% placebo), rash (15% vs. <1% placebo), and diarrhea (9% vs. none placebo); Sutent was associated with increased incidence of fatigue (18% vs. 3% placebo), hand-foot syndrome (33% vs. 1% placebo), and diarrhea (10% vs. none placebo). The majority of worst degree of all event types was considered to be Grade 3 adverse events (67% Nexavar, 57% Sutent, 20% placebo), which were non-life-threatening but required medical intervention.

    With the lack of even a trend to efficacy benefit and significant high-grade toxicity for both Nexavar and Sutent, the initial results of ASSURE do not support any use of these two drugs in the adjuvant setting for RCC. In light of the lack of effective adjuvant therapies for RCC, the outcomes of ASSURE will be further assessed to determine whether VEGF TKI therapy may be effective in a subset of intermediate- and very high-risk RCC patients. One point of interest that wasn’t reported in the ASCO GU presentation was the effect of dose, dose-reduction and drop-out rate on clinical efficacy. These analyses are being conducted now and hope to be reported at a future conference.

    The ASSURE trial adds to the growing body of evidence that targeted therapeutics approved in the metastatic setting may not provide clinical benefit in the adjuvant setting. Other notable failures include Avastin® (bevacizumab, Genentech/Roche/Chugai) in adjuvant colon cancer4 and Erbitux® (cetuximab, Lilly/BMS/Merck KGaA) in adjuvant colon cancer.5 Not all targeted therapeutics have failed to improve efficacy in the adjuvant setting – Yervoy® (ipilimumab, BMS) improved DFS in melanoma, and Gleevec® (imatinib, Novartis) improved DFS in gastrointestinal stromal tumor – so it raises the question of whether the observed failures are due to ineffective agents or ineffective mechanisms of action. Nexavar and Sutent, while multitargeted, are considered anti-angiogenic in nature, as is Avastin; the failure of all three agents to improve DFS in the adjuvant setting suggests that anti-angiogenesis is not an effective approach to treatment and prevention of recurrence in the non-metastatic setting. In the example of Avastin in colon cancer, landmark analysis showed a clinical benefit for the period of time during which Avastin was being administered, but the benefit eroded after Avastin treatment was ceased. A similar effect appears to have occurred in the ASSURE trial; in the Kaplan Meyer curve for DFS, the Sutent and Nexavar arms were both overlapping and clearly separated from the placebo arm from approximately six months until approximately 20 months.

    These trials raise the question of what the appropriate duration of therapy for an anti-angiogenic therapy in the adjuvant setting is. This issue is being explored in the ongoing SORCE study (NCT00492258), which is comparing placebo vs. Nexavar for one year or three years in resected clear cell and non-clear cell RCC patients. The ATLAS study (NCT01599754) is also exploring prolonged adjuvant therapy for another anti-angiogenic agent, Inlyta® (axitinib, Pfizer) by comparing placebo vs. Inlyta for three years in very high-risk (as scored by UISS criteria), clear cell RCC patients. These studies may provide answers to whether prolonged duration of treatment is necessary to observe a clinical benefit in these patients. However, even if these trials show a benefit with prolonged administration, the tolerability of these agents is still in question. In the meantime, the results of ASSURE support a change of treatment practice – the significant off-label use of Nexavar and Sutent (and by extension other VEGFR TKIs) in Stage I-III RCC should be ceased. With this, the level of unmet need for high-risk, early-stage RCC remains high, and determining the best treatment approach for this disease is anxiously awaited.

    References:

    1. Lam JS, Shvarts O, Leppert JT, et al. “Renal cell carcinoma 2005: new frontiers in staging, prognostication and targeted molecular therapy.” J Urol. 2005;173:1853-62.
    2. Kantar Health, CancerMPact® Treatment Architecture U.S., accessed February 27, 2015.
    3. Haas NB, Manola J, Uzzo RG, et al. “Initial results from ASSURE (E2805): Adjuvant sorafenib or sunitinib for unfavorable renal carcinoma, an ECOG-ACRIN-led, NCTN phase III trial.” In American Society of Clinical Oncology Genitourinary Cancers Symposium; February 28, 2015; Orlando, Florida. Abstract 403.
    4. Allegra CJ, Yothers G, O’Connell MJ, et al. “Phase III trial assessing bevacizumab in stages II and III carcinoma of the colon: results of NSABP protocol C-08.” J Clin Oncol. 2011;29(1): 11-16.
    5. Huang J, Nair SG, Mahoney MR, et al. “Comparison of FOLFIRI with or without cetuximab in patients with resected stage III colon cancer; NCCTG (Alliance) intergroup trial N0147.” Clin Colorect Canc. 2014;13(2): 100-109.

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

    HIGHLIGHTS OF 2015 GU CANCERS SYMPOSIUM

    Experts from all over the world are gathering to tackle challenges in managing prostate, kidney, bladder, testicular, and other genitourinary (GU) cancers at the 2015 Genitourinary Cancers Symposium in Orlando, Florida, February 25-28th.

    A pre-meeting Presscast gave a sneak preview of five important studies to be presented at the meeting.

    AR-V7 Potential Marker for Chemotherapy Sensitivity

    A small study of 37 men found that an androgen receptor (AR) abnormality called AR-V7 appears to predict for sensitivity to taxanes (docetaxel and cabazitaxel) in men with metastatic castration-resistant prostate cancer (CRPC). This study comes on the heels of a previous study by the same group showing that the presence of AR-V7 in circulating tumor cells predicts resistance to hormone therapy with enzalutamide and abiraterone.

    The field of prostate cancer lags behind breast cancer and other cancers where predictive markers have been identified. Results of the two studies by this group, taken together, suggest that AR-V7 positive patients with metastatic CRPC should be offered chemotherapy as initial therapy, rather than AR-directed hormone therapy, while those who are AR-V7 negative can be safely treated with either regimen.

    “We urgently need markers which predict which therapies are going to be effective and which will not … in individual patients with prostate cancer. AR-V7 testing may be extremely valuable in guiding treatment decisions for men with hormone-resistant disease in the near future,” said lead author Emmanuel Antonarakis, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, MD. He noted that as yet there is no commercially available CLIA-certified test for AR-V7, “but we and others are working on that.”

    Based on these data, which need validation in a prospective, multicenter trial, Dr. Antonarakis said that the test for AR-V7 appears to be of greater utility for positive patients. The AR-V7 abnormality is thought to occur in about one third of patients with CRPC.

    Testicular Cancer Linked to Aggressive Prostate Cancer

    A history of testicular cancer increases the likelihood of developing intermediate- and high-risk prostate cancer, according to a case-control study of about 180,000 men. By age 80, the study showed that prostate cancer developed in 12.6% of men with a history of testicular cancer compared with 2.8% of those with no such history. The incidence of intermediate- or high-risk prostate cancer was 5.8% versus 1.1%, respectively.

    Overall, a history of testicular cancer was associated with a 4.7 times higher risk of prostate cancer and 5.2 times higher risk of intermediate- or high-risk disease.

    “This study should alert men with a history of testicular cancer [and other risk factors for prostate cancer] to have a discussion with their doctor about assessment of risk of prostate cancer,” said senior study author Mohummad Minhaj Siddiqui, MD, University of Maryland School of Medicine and director of urologic robotic surgery at the University of Maryland, Marlene and Stewart Greenebaum Cancer Center in Baltimore, MD.

    Dr. Siddiqui noted that the link between a history of testicular cancer and the development of prostate cancer has been previously reported, but the new finding is the increased risk of intermediate- and high-risk prostate cancer. He said that further research is needed on the biologic link between these two diseases.

    The absolute risk of developing intermediate- or high-risk prostate cancer was low: 95% of men who have had testicular cancer will not develop it, said Dr. Siddiqui.

    The study was based on SEER (Surveillance, Epidemiology, and End Results) data that included 32,435 men with a history of testicular cancer and 147,044 men with a history of melanoma. Melanoma was chosen as the control group, because it has no known association with prostate cancer.

    Intermediate-Risk Prostate Cancer and Active Surveillance

    Patients with intermediate-risk (IR) prostate cancer fare far worse than those with low-risk prostate cancer when managed with active surveillance. In fact, IR patients managed with active surveillance had almost a four times higher risk of prostate cancer-specific death over 15 years compared with low-risk patients. These were the findings of the first study to analyze long-term outcomes of patients with IR prostate cancer managed by active surveillance.

    “This study validates active surveillance for low-risk patients with prostate cancer. We were surprised by the greater risk of prostate cancer death in the IR patients assigned to active surveillance,” stated presenting author, D. Andrew Loblaw, MD, Sunnybrook Health Sciences Center in Toronto, Canada.

    Data were collected prospectively on 945 patients: 237 with IR and 708 with low-risk prostate cancer managed with active surveillance between 1995 and 2013 at Sunnybrook Health Sciences Center. Radiation or surgery was offered for disease progression, and 86 IR patients were treated.

    Ten-year and 15-year overall survival (OS) rates were 68.4% and 50.3% for IR patients compared with 83.6% and 68.8% for low-risk patients. Dr. Loblaw noted that 60% of the IR patients were older than age 70, and men in the IR category in general had short life expectancies due to other comorbidities.

    Overall, IR patients had a 3.75 times higher risk of prostate cancer-specific death at 15 years compared with low-risk patients (11.5% versus 3.7%, respectively).

    Charles Ryan, MD, moderator of the Presscast, said that further sub-categorization of IR patients based on molecular and/or clinical markers is an ongoing area of study. Dr. Ryan is an ASCO Expert and GU News Planning Team Member.

    “We think there may be a subgroup of IR patients out there who may be safely managed by active surveillance,” Dr. Loblaw said. “Further research is needed to better characterize those patients.”

    PSA Screening for Prostate Cancer Revisited?

    Between 2009 and 2011, the incidence of higher-risk prostate cancer has increased by almost 6%, leading to an estimated 1400 additional prostate cancer-specific deaths 10 years later, according to a retrospective study of 87,562 men diagnosed with prostate cancer between January 2005 and June 2013. The authors state that further research is needed to confirm these findings.

    The year 2011 corresponds to the U.S. Preventive Services Task Force (USPSTF) draft recommendation against PSA screening for all men in the general population. One interpretation of the study findings is that implementing these recommendations led to identification of prostate cancer at a more advanced stage.

    “Our study is the first to measure changes in prostate cancer presentation in the period following the USPSTF PSA screening recommendations. Given the findings of our analysis in this time frame, men who are at increased risk for prostate cancer, especially those with a family history of prostate cancer, should consider talking with their doctor about PSA screening,” said lead author Timothy F. Schultheiss, PhD, City of Hope, Duarte, CA.

    “We can only speculate about whether the USPSTF recommendations are responsible [for the increase in higher risk cases being diagnosed], but we believe that the USPSTF might reconsider their recommendation,” he further stated.

    Dr. Ryan said: “This study adds to the ongoing debate about PSA screening and underscores the importance of reconsidering guidelines.”

    Don’t Change Standard of Care for Locally Advanced Kidney Cancer

    Adjuvant sorafenib and sunitinib did not improve disease-free survival (DFS) in patients with locally advanced kidney cancer who are at high risk of recurrence. These results of the first and largest study on the efficacy of adjuvant VEGF inhibitors (sorafenib and sunitinib) in this setting suggest that the standard of care for these patients should remain close observation.

    “No one could be more disappointed in these results than me, except for the patients with kidney cancer. Even though these drugs provide benefit in the metastatic setting, they did not reduce disease recurrence in the adjuvant setting, and they did increase side effects,” said lead author Naomi B. Hass, MD, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA.

    Ongoing analysis of tumor specimens collected during the trial may help identify subsets of patients who might benefit from VEGF inhibitors in the adjuvant setting, she said.

    The study included 1943 patients who underwent surgery and were deemed high risk for recurrence based on tumor size, grade, and lymph node involvement. Patients were randomized to receive sorafenib, sunitinib, or placebo for 1 year.

    Interim analysis revealed similar rates of recurrence in all three groups (around 40%) and similar rates of DFS (5.6 – 5.7 years). Final analysis of recurrence and survival will be presented in the future.

    Other adjuvant trials of axitinib (a VEGF inhibitor) and everolimus (mTOR inhibitor) are accruing patients, and adjuvant trials of immunotherapy and other targeted approaches are under development.

    “The fact that this is a negative trial no way diminishes its importance. Tyrosine kinase inhibitors [VEGF inhibitors] may not be as effective as chemotherapy in the adjuvant treatment of solid tumors,” Dr. Ryan stated. “This study supports my current practice of not using these drugs in the adjuvant setting.”

    By Alice Goodman

    ABSTRACT NUMBERS FOR REFERENCE:

    • AR-V7. [Abstract 138]
    • Testicular cancer and prostate cancer. [Abstract 177]
    • Active surveillance of intermediate-risk prostate cancer [Abstract 163]
    • Increase in higher-risk prostate cancers following USPSTF 2011 recommendations for PSA screening. [Abstract 143]
    • Adjuvant sorafenib and sunitinib for locally advanced kidney cancer. [Abstract 403]

    Syndicated Post-SABCS 2014 OncoPoll™: Global Breast Cancer Disease Landscape

    Introduction

    In an effort to provide you with timely market feedback from SABCS 2014, OBR and MDoutlook® are pleased to share results from MDoutlook’s OncoPoll from the meeting. This report explored the impact of new data presented at SABCS 2014.

    OncoPoll™ Methodology

    • Primary research phase involved a global survey to MDoutlook’s panel of verified and validated medical oncologists screened for patient volume in breast cancer
    • Timing: December 2014. Launched three days after close of SABCS 2014, held in San Antonio, Texas December 9 – 13, 2014
    • Reponses at data collection: 125 respondents representing 15 countries
      • 41 US respondents
      • 15 German respondents
      • 14 French respondents
      • 15 Italian respondents
      • 15 Spanish respondents
      • 25 Rest of Europe (ROE) respondents

    Attendance at SABCS 2014

    Key Conclusions

    • Nearly a 50/50 split of Italian, Spanish, and ROE respondents attended the SABCS 2014
    • The majority of US survey respondents attended SABCS 2014

    Survey Participants’ Breast Cancer Patient Flow: Average Over 20 Early and Metastatic Breast Cancer Cases Each Quarter

    Key Conclusion

    • The largest proportion of mBRCA patients treated by respondents are HER2- HR2+ (30-60%)

    Assessment of New Agents in Breast Cancer Pipeline: Cumulatively, Physicians Assess New Agents Pembrolizumab and MPDL3280A to Potentially Have Largest Clinical Impact on Breast Cancer Patients

    Key Conclusions

    • Of the 13 new agents listed, pembrolizumab (anti-PD-1 mAb; S1-09) (35%) and MPDL3280A (anti-PD-1L; PD1-6) (31%) have the highest proportion of physicians who project they will have a “large impact for many patients”
    • However, for each new agent listed, the highest proportion of physicians project they will have a “large impact for few patients”
    • All new agents also have 2%-15% of physicians who project they will have “little to no value”

    Adjuvant Therapy

    NSABP B-36 Trial (Phase 3)

    Clinical Impact NSABP B-36 Trial on Adjuvant Therapy: Usage of 4 Cycles of AC Projected To Grow (Except U.S.) – Usage of 6 Cycles of FEC Projected to Decrease (Except U.S.)

    Key Conclusions

    • Unlike in Europe, U.S. physicians project to increase usage of 6 cycles of FEC (11% to 20% of patients) and slightly decrease (44% to 43% of patients) usage of 4 cycles of AC adjuvant therapy for node-negative breast cancer patients
    • Overall, European physicians plan to decrease the usage of 6 cycles of FEC and increase the usage of 4 cycles of AC as adjuvant therapy

    Supportive Care

    Febrile Neutropenia (FN) In Breast Cancer: Approximately 1 in 8 Breast Cancer Patients Develop Febrile Neutropenia

    Key Conclusions

    • U.S. and ROE physicians report on average 15% of their patients develop FN
    • All other countries report 9% – 12% of their patients develop FN

    Current Treatment for FN


    Key Conclusions

    • U.S. is only country where pegfilgrastim is used on more patients (50%) then filgrastim (44%) as a treatment for FN
    • In all other countries, filgrastim is used on more patients at approximately 60% / 40% split.
    • Very few patients are receiving other treatments for FN. Other treatments include:
      • Leukine (US), Granix (US), and ROE physicians indicated “no primary GCSF prophylaxis”

    Respondents Overwhelmingly Expect to Prescribe Biosimilar GCSF if Approved by FDA

    Key Conclusions

    • 90+% of German and Italian respondents and ~80% of US and French physicians project they will prescribe a biosimilar GCSF if approved by FDA
    • 60+% of Spanish and ROE physicians expect to prescribe a biosimilar GCSF if approved
    • Physicians saying no: U.S. (9%), ROE (25%), Spain (20%) and Italy (8%)
    To download a copy of this analysis report or to get more information on the full SABCS2014 analysis report that expands on these topics and delivers much more – including the impact of additional SABCS data announcements on physician awareness, their clinical assessment of the potential impact of these therapies & projected future clinical utilization, please click here.

    Submitted by Jessica Harnisch, Assoc. Global Medical Analyst; Raj Manimaran, Global Medical Analyst; Robert Stephan, Sr. Director Medical Services and Strategy; Craig Krugman, Sr. Vice President; and Jan Heybroek, President.

    CMMI’s Oncology Care Model (OCM) – Is it Right for Your Organization?

    Yesterday, February 12, 2015, the Center for Medicare and Medicaid Innovation (CMMI) announced the long anticipated launch of its newest payment and services delivery model, the Oncology Care Model (OCM). OCM is a 5-year initiative intended to create incentives to furnish efficient, high quality care by enhancing services for Medicare fee-for-service (FFS) beneficiaries undergoing chemotherapy treatment for cancer diagnosis, while at the same time, lowering the overall costs of care for those same beneficiaries. OCM covers virtually all cancer types. The application deadline for participation in OCM is June 18, 2015 with an anticipated actual commencement of OCM in spring 2016.

    Qualified OCM applicants will be “physician group practices and practitioners in solo practice (collectively “practices”) that provide care for oncology patients undergoing chemotherapy for cancer.” The definition of a qualified participant is important. In CMMI’s original August 2014 release of its concept piece for OCM, “Preliminary design for an oncology-focused model,” CMMI proposed that OCM participants would be “physician practices that furnish chemotherapy treatment.” Subsequently CMMI was advised that, taken literally, this definition would exclude some 40% to 50% of all practicing oncologists nationally, those providing cancer services as employees of or in collaborative contractual relationships with hospitals/health systems or academic medical centers. Recognizing that oncologists working with/for institutions should not be excluded from OCM participation, the revised definition of participant deletes reference to “furnish” chemotherapy, thus opening OCM enrollment to oncologists (“practices”) that provide cancer care services as employees of or in collaboration with institutions. We believe that an OCM undertaking by such organizations will be the foundation for evaluating true cost of care (rather than solely claims history) and enable providers to prepare for fixed pricing across the full continuum of cancer care (bundled pricing, case rates, for example).

    Other key features of OCM include: 

    1. Participating practices must meet certain requirements, such as incorporating care coordination, 24-hour access to practitioners who can consult the patient’s medical record in real time, issue comprehensive patient care plans, provide patient navigators and demonstrate continuous quality improvement – essentially the principals of the oncology medical home model;
    2. Participating practices will receive two types of payment (in addition to routine FFS claims): (i) a $160 per beneficiary per month (PBPM) care management fee for FFS Medicare beneficiaries during the 6-month period commencing with the initial chemotherapy treatment plus (ii) a performance-based payment based on demonstration of quality improvement and overall cost of care. OCM will apply a retrospective pricing model to determine the baseline from which cost reduction will be calculated.
    3. CMMI expects OCM to be a multi-payer model with other payers, particularly commercial health insurers, working in tandem with Medicare to promote care process re-design and cost reduction across all patient populations.

    Is OCM right for your organization? Oncology providers are cautioned to first consider whether OCM is appropriate for their organization before applying. Is the organization ready to undertake the process re-designs and cultural change inherent in OCM? Are the financial implications of OCM positive for your organization? What are the ramifications to your organization of not participating in OCM?

    For more on OCM strategy, evaluation and application design contact the author, Ronald Barkley, MS, JD, President, Cancer Center Business Development Group at rbarkley@ccbdgroup.com or 603-472-2285.

    Syndicated Post-ASH 2014 MDoutlook® OncoPolls™: Insight Into the Global Hematological Oncology Disease Landscape: CLL, ALL, Multiple Myeloma

    Introduction

    In an effort to provide you with timely physician feedback from ASH 2014, OBR and MDoutlook are pleased to share results from MDoutlook OncoPoll surveys fielded immediately after the meeting. This report explores the impact of new data in CLL, ALL, and Multiple Myeloma presented at ASH 2014, held in San Francisco, California, December 6 – 9, 2014.

    2014 Post-ASH OncoPoll: Chronic Lymphocytic Leukemia (CLL)

    MDoutlook OncoPoll Methodology

    • Primary research phase involved a global survey to MDoutlook’s proprietary U.S. and European panel of verified and validated hematological oncologists screened for patient volume in CLL
    • Timing: December 2014. Launched three days after close of ASH 2014
    • Reponses at data collection: 150 respondents – representing 18 countries

    o 43 US respondents

    o 20 German respondents

    o 17 French respondents

    o 21 Italian respondents

    o 19 Spanish respondents

    o 30 Rest of Europe (ROE) respondents

    CLL Patient Volume in Past 3 Months

    Assessment of the Clinical Importance & Concept of Anti-CD20 Antibodies Maintenance Therapy for CLL Patients

    Key Conclusions

    • Countries with the highest regard that anti-CD20 antibodies used in 1st line will become standard clinical practice in CLL MT: Germany (44%), Spain (42%), and France (41%)
    • Countries with the highest regard that MT with anti-CD20 antibodies will not become standard practice: U.S. (43%), France (41%), and Germany (33%)
    • Countries with the highest regard that using a different anti-CD20 antibody from that used in 1st line will become standard clinical practice in CLL MT: Italy (44%), Spain (32%) and ROE (28%)

    Impact of Presentations on Tyrosine Kinase Inhibitors Ibrutinib and Idelalisib for the Treatment of CLL

    Key Conclusion

    • 90%-100% of all respondents rated the clinical importance of the information in this abstract 4 or 5 (on 5pt scale)

    Key Conclusion

    • 80%-100% of all respondents rated the clinical importance of the information in this abstract 4 or 5 (on 5pt scale)

    2014 ASH OncoPoll: Acute Lymphocytic Leukemia (ALL)

    MDoutlook OncoPoll Methodology

    • Primary research phase involved a global survey to MDoutlook proprietary U.S. panel of hematological oncologists screened to verify they managed at least 1 ALL patient aged ≥16 years old in the last 12 months
    • Timing: December 2014. Launched three days after close of ASH 2014
    • Reponses at data collection: 77 US respondents

    Survey Participants’ Practice Setting and ASH Meeting Attendance

    Respondent Characteristics and ALL Patient Volume

    Key Conclusion

    • Respondents averaged 20 ALL patients in last 12 months

    BLAST Study (Phase 2): Evaluation of Blinatumomab (MT103) for the Treatment of ALL Patients with Minimal Residual Disease

    Key Conclusions

    • Based upon Phase 2 BLAST study results, physicians project they will place 23% of their 1st line and 51% of their 2nd line relapsed or refractory B-Cell precursor patients on blinatumomab
    • By 3rd and 4th line, physicians project they will place ~60% of their relapsed or refractory B-Cell precursor patients on blinatumomab

    2014 ASH OncoPoll: Multiple Myeloma (MM)

    MDoutlook OncoPoll Methodology

    • Primary research phase involved a global survey to MDoutlook panel of hematological oncologists screened for patient volume in multiple myeloma
    • Timing: December 2014. Launched three days after close of ASH 2014
    • Reponses at data collection: 127 respondents representing 35 countries

    o 43 US respondents

    o 40 EU5 respondents

    o 27 Rest of Europe (ROE) respondents

    o 17 Rest of World (ROW) respondents

    Respondent Practice Classification and Meeting Attendance