Eligibility Criteria and Endpoints in Metastatic Renal Cell Carcinoma Trials.

OBJECTIVES: Treatments for metastatic renal cell carcinoma (mRCC) are often compared across trials, but trial eligibility criteria and endpoints differ. In an effort to better align trials, the Definition for the Assessment of Time to event Endpoints in CANcer trials (DATECAN) project published recommendations in 2015 to be used in mRCC clinical trial design. We analyzed mRCC trial criteria to determine if DATECAN's recommendations were followed. MATERIALS AND METHODS: We compared eligibility criteria across 29 phase 3 mRCC trials conducted between 2003 and 2019. We then evaluated endpoints used in 10 phase 3 trials activated between 2015 and 2019 to determine their compliance with DATECAN's recommendations. RESULTS: Among the 29 trials, performance status, renal function, and disease characteristics differed in terms of requirements and measures used. In terms of endpoints, the 10 trials did not entirely follow DATECAN's recommendations. In total, 7/10 trials' primary endpoint was progression-free survival (PFS) as recommended; 4/9 trials used PFS as an endpoint but did not publish their definition of PFS, and the 5 that did, included "death from any cause" instead of DATECAN's recommendation of "death from kidney cancer." CONCLUSIONS: Key eligibility criteria were somewhat inconsistent across the phase 3 mRCC trials studied. Endpoints in the newer trials did not align with DATECAN's recommendations. Not only is greater standardization needed to facilitate meta-analyses and cross-trial comparisons, but as evident from lack of adherence to DATECAN's recommendations, greater promotion and adoption of recommendations are needed to better harmonize trial design.

Application of the ASCO Value Framework and ESMO Magnitude of Clinical Benefit Scale to Assess the Value of Abiraterone and Enzalutamide in Advanced Prostate Cancer.

PURPOSE: As novel hormonal therapies, such as abiraterone and enzalutamide, move into earlier stages of treatment of advanced prostate cancer, there are significant cost implications. We used the ASCO Value Framework (AVF) and European Society of Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale (MCBS) to quantify and compare the incremental clinical benefit and costs of these agents in the metastatic castration-resistant prostate cancer (mCRPC) and metastatic castration-sensitive prostate cancer (mCSPC) settings. METHODS: We searched PubMed for randomized phase III trials of abiraterone and enzalutamide in mCRPC and mCSPC. Incremental clinical benefit was quantified using the AVF and ESMO-MCBS by 2 independent assessors. Incremental drug costs were calculated using average wholesale prices (AWPs) from the RED BOOK Online. RESULTS: In mCRPC, 2 abiraterone trials (COU-AA-301 and COU-AA-302) and 2 enzalutamide trials (AFFIRM and PREVAIL) met search criteria. AVF scores ranged from 46.3 to 66.6, suggesting clinical benefit; ESMO-MCBS scores ranged from 3 to 5, with lower clinical benefit in the mCRPC predocetaxel setting. The overall incremental AWP ranged from $83,460.94 to $205,128.85. In mCSPC, 4 trials met criteria (LATITUDE, STAMPEDE, ENZAMET, and ARCHES; AVF scores were 79.8, 33.3, 59, and 17, respectively). All of the studies showed benefit except ARCHES. By ESMO-MCBS, both LATITUDE and STAMPEDE showed benefit (score for 4 for both studies); ENZAMET and ARCHES were not evaluable. The overall cost of treatment was significantly higher in the mCSPC setting. CONCLUSION: The AVF and ESMO-MCBS frameworks generated slightly different results but suggested that abiraterone and enzalutamide show clinical benefit in both mCRPC and mCSPC but trended to lower clinical benefit and increased costs in earlier disease stages. Further refinement of the AVF and ESMO-MCBS is needed to facilitate their use and their ability to inform clinical practice in a rapidly changing treatment landscape.

Screen Failure Rates in Contemporary Randomized Clinical Phase II/III Therapeutic Trials in Genitourinary Malignancies.

BACKGROUND: Screen failures, defined as individuals who undergo screening but are not enrolled in a clinical trial, incur significant costs without contributing valuable data to the study. Despite these costs, there are few published data about the rate or reasons for screen failures in advanced genitourinary cancer clinical trials. MATERIALS AND METHODS: We reviewed 50 phase II and III trials in advanced genitourinary cancers conducted between 1999 and 2016. RESULTS: Of the 50 trials, only 48% (24 of 50) published screen failure rates: 68% (13 of 19) of those in prostate cancer, 33% (6 of 18) in kidney cancer, and 58% (5 of 13) in bladder cancer. Among the phase III trials in prostate cancer, the mean screen failure rate was 26% (range, 12%-45%). The main reason for screen failure was reported as ineligibility. Among the phase III trials in kidney cancer, the mean screen failure rate was 25% (range, 21%-29%), with the most frequent reasons being ineligibility and patient refusal. Among the phase II/III trials in bladder cancer, the mean screen failure rate was 19% (range, 4%-28%), with the main reasons being ineligibility and patient refusal. CONCLUSION: Contemporary trials in genitourinary cancer reported screen failure rates of approximately 20% to 30%. Many trials did not report on the numbers of, and reasons for, screen failures. Greater standardization of definitions, methods, and reporting are needed to better understand and decrease screen failure rates in genitourinary cancer clinical trials.