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]
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.
Attendance at SABCS 2014
Survey Participants’ Breast Cancer Patient Flow: Average Over 20 Early and Metastatic Breast Cancer Cases Each Quarter
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
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.)
Febrile Neutropenia (FN) In Breast Cancer: Approximately 1 in 8 Breast Cancer Patients Develop Febrile Neutropenia
Current Treatment for FN
Respondents Overwhelmingly Expect to Prescribe Biosimilar GCSF if Approved by FDA
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:
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 email@example.com or 603-472-2285.
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
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
Impact of Presentations on Tyrosine Kinase Inhibitors Ibrutinib and Idelalisib for the Treatment of CLL
2014 ASH OncoPoll: Acute Lymphocytic Leukemia (ALL)
MDoutlook OncoPoll Methodology
Survey Participants’ Practice Setting and ASH Meeting Attendance
Respondent Characteristics and ALL Patient Volume
BLAST Study (Phase 2): Evaluation of Blinatumomab (MT103) for the Treatment of ALL Patients with Minimal Residual Disease
2014 ASH OncoPoll: Multiple Myeloma (MM)
MDoutlook OncoPoll Methodology
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
Multiple Myeloma Patient Volume
ASPIRE Trial (Phase 3): Evaluation of Carfilzomib, Lenalidomide, and Dexamethasone vs. Lenalidomide and Dexamethasone in Relapsed Multiple Myeloma