Dr Grivas on Future Directions for Adjuvant Therapy Research in RCC

Petros Grivas, MD, PhD, professor, Clinical Research Division, Fred Hutchinson Cancer Center; professor, Division of Hematology and Oncology, University of Washington (UW) School of Medicine; clinical director, Genitourinary Cancers Program, UW Medicine, discusses potential future directions for research with adjuvant therapy in patients with resected renal cell carcinoma (RCC).

During an OncLive® State of the Science Summit™ on genitourinary cancer, which Grivas co-chaired, Lisa Tachiki, MD, of Fred Hutchinson Cancer Center, gave a presentation about clinical trials that have investigated TKIs as well as immunotherapy regimens in patients with RCC, particularly in patients with clear cell RCC (ccRCC). At the event, Tachiki, Grivas, and colleagues emphasized the need for additional research in non-ccRCC.

The phase 3 KEYNOTE-564 trial (NCT03142334) demonstrated a disease-free survival (DFS) and overall survival advantage with pembrolizumab (Keytruda) compared with placebo in patients with ccRCC. These findings supported the 2021 FDA approval of adjuvant pembrolizumab for patients with RCC at high or intermediate-high risk of recurrence after nephrectomy with or without resection of metastatic lesions.

However, several recent trials of adjuvant immunotherapy in RCC did not meet their primary end points for a variety of reasons, Grivas says. In the phase 3 CheckMate 914 trial (NCT03138512), adjuvant nivolumab (Opdivo) plus ipilimumab (Yervoy) did not improve DFS compared with placebo in patients with localized, high-risk, resected RCC. Additionally, the phase 3 IMmotion010 trial (NCT03024996) demonstrated that adjuvant atezolizumab (Tecentriq) did not improve clinical outcomes vs placebo in patients with high-risk, resected RCC. Furthermore, the phase 3 PROSPER-RCC trial (NCT03055013) showed that perioperative nivolumab elicited no recurrence-free survival improvement vs surgery alone in patients with high-risk RCC. The findings from these trials have dampened enthusiasm for adjuvant immunotherapy for patients with RCC, Grivas notes.

However, data from the KEYNOTE-564 trial may revitalize interest in and excitement for investigations of adjuvant immunotherapy in this patient population, Grivas emphasizes. This well-designed trial and the subsequent FDA approval of adjuvant pembrolizumab support the widespread use of this therapy in patients with resected RCC at high risk for recurrence, Grivas explains.

Ongoing and upcoming clinical trials are investigating the potential use of adjuvant combination therapies for patients with RCC, according to Grivas. More combination trials and additional biomarkers are needed to enhance the adjuvant RCC treatment paradigm, Grivas concludes.