Assessment of eligibility criteria in renal cell carcinoma trials evaluating systemic therapy

Abstract

ObjectivesTo characterize the restrictiveness of eligibility criteria in contemporary renal cell carcinoma (RCC) trials, using recommendations from the American Society of Clinical Oncology (ASCO)‐Friends of Cancer Research (FCR) initiative.MethodsPhase I‐III trials assessing systemic therapies in patients with RCC starting between June 30, 2012 and June 30, 2022 were identified. Eligibility criteria regarding brain metastases, prior or concurrent malignancies, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, and human immunodeficiency virus (HIV) infection were identified and stratified into 3 groups: exclusion, conditional inclusion, and not reported. Descriptive statistics were used to determine the frequency of eligibility criteria. The Fischer's exact test or Chi‐square test were performed to calculate their associations with certain trial characteristics.Results423 RCC trials were initially identified of which 112 (26.5%) had sufficient accessible information. Exclusion of patients with HIV infection, HBV/HCV infection, brain metastases, and prior or concurrent malignancies were reported in 74.1%, 53.6%, 33.0%, and 8.0% of trials, respectively. In the context of HIV and HBV/HCV infection, patients were largely excluded from trials evaluating immunotherapy (94.4% and 77.8%, respectively). In addition, brain metastases were excluded in trials assessing targeted therapy (36.4%), combination therapy (33.3%), and immunotherapy (22.2%). Exclusion of patients with prior or concurrent malignancies was less frequently reported, accounting for 9.1%, 8.3%, and 5.6% targeted, combination and immunotherapy trials, respectively.ConclusionA substantial proportion of RCC trials utilize restrictive eligibility criteria, excluding patients with fairly prevalent comorbidities. Implementing the ASCO‐FCR recommendations will ensure resulting data is more inclusive and aligned with patient populations in the real‐world.

An Overview of Systemic Targeted Therapy in Renal Cell Carcinoma, with a Focus on Metastatic Renal Cell Carcinoma and Brain Metastases

“…Regarding patients with BM RCC, eligibility criteria in RCC trials are even more problematic. Recent studies report that approximately 33-38% of RCC clinical trials excluded patients with BM [135,137], while 62% included these patients only if the BM were not active [135]. Furthermore, most VEGFR TKI (for progression on combination of ICI (e.g., Nivolumab, Ipilimumab), and for patients who progress on ICI + VEGFR TKI.…”

“…Regarding patients with BM RCC, eligibility criteria in RCC trials are even more problematic. Recent studies report that approximately 33-38% of RCC clinical trials excluded patients with BM [135,137], while 62% included these patients only if the BM were not active [135]. Furthermore, most studies exclude patients with BM RCC treated with prior glucocorticoids for brain edema, as this treatment will reduce the blood-brain barrier (BBB) permeability of systemic agents [79] Consequently, accrual rates are low, and the results have poor generalizability.…”