IKCS 2022: Critical Assessment of Eligibility Criteria in Contemporary Renal Cell Carcinoma Trials Evaluating Systemic Therapy

(UroToday.com) The eighth session of the 2022 International Kidney Cancer Symposium (IKCS): North America meeting focused on regulatory considerations for new trials in advanced renal cell carcinoma (RCC). In this context, Daniela Castro presented a critical assessment of eligibility criteria among clinical trials evaluating systemic therapy in patients with renal cell carcinoma (RCC).

By way of background, she noted that a joint statement from the Friends of Cancer Research (FCR) and the American Society of Clinical Oncology (ASCO) highlighted the need to broaden eligibility criteria in cancer trials to increase patient accrual and enhance the generalizability of study results. However, the degree to which modern trials adhere to this principle is unclear.

In this study, the authors sought to characterize the frequency of exclusionary criteria in RCC trials deemed by the FCR-ASCO statement to be potentially excessive. To do so, they used ClinicalTrials.gov to identify studies with start dates from June 30, 2012 to June 30, 2022 using the following criteria: “(metastatic OR advanced OR stage IV OR unresectable) AND (kidney cancer OR renal cell carcinoma OR renal cell cancer)”. They identified international studies examining patients age ≥ 18 in phase I-III trials. They excluded pan-cancer studies and trials involving localized treatments, prognostic tools, or radiation therapy.

The authors identified 423 trials among patients with RCC. Among these, 112 (26.5%) had sufficient publicly available data for evaluation. Over one-third of studies (44, 39.3%) evaluated targeted therapy, 18 (16.1%) evaluated immunotherapy, and (48; 42.9%) evaluated combination therapy.

The most frequently cited exclusionary criteria were the presence of hepatitis B/C positivity (91 of 91 trials, 100.0%), concurrent malignancies positivity (90 of 90 trials, 100.0%), HIV positivity (91 of 92 trials, 98.9%), and brain metastases (90 of 101 trials, 89.1%).

Ms. Castro presented then on each of these four criteria individually. Examining HIV specifically, she noted that the majority of trials included this as a exclusion criteria, particularly in trials of chemotherapy, immunotherapy and combination therapy and substantially less so in trials of targeted therapy. In the context of Hepatitis B and C, she noted that conditional inclusion (rather than full exclusion) was substantially more common than was observed for HIV. For patients with brain metastasis, similarly, conditional inclusion was similarly fairly common with many trials allowing patients with previously treated brain metastases provided that these are stable without evidence of new or enlarging brain metastases. Finally, in the context of concurrent malignancies, total exclusion was relatively uncommon though most studies had conditional inclusion such as a restriction of patients to those with adequately treated skin cancers, non-invasive bladder cancer, or other Stage 1 or 2 cancer currently in complete remission.

Over the 10-year evaluation period, no significant trend was observed in use of these exclusionary criteria, nor were any significant differences observed in the use of these criteria among trials based on drug class.

The authors concluded that a substantial proportion of contemporary RCC studies incorporate exclusionary criteria deemed by the FCR-ASCO statement to be potentially excessive or restrictive. Broadening eligibility criteria will ensure that the resulting data is representative of real-world patient populations.