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  • 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

    Key Conclusions

    • The majority of US respondents practice in a community setting (69%) and did not attend ASH (60%)
    • A slight majority of ex-US respondents practice in an academic setting (54%) and did not attend ASH (52%)

    Multiple Myeloma Patient Volume