Dr Rini on Retreatment With Immunotherapy Following Progression in RCC

Brian I. Rini, MD, FASCO, professor of medicine, Division of Hematology Oncology, chief of Clinical Trials, Vanderbilt-Ingram Cancer Center, discusses the investigation of immunotherapy following disease progression on previous immunotherapy in patients with relapsed/refractory renal cell carcinoma (RCC).

One of the most pressing questions across the RCC treatment landscape is whether immunotherapy could still play a role in the treatment of patients following progression on a prior immune checkpoint inhibitor, Rini begins. Data from a phase 1/2 trial (NCT02501096) showed the combination of lenvatinib (Lenvima) and pembrolizumab (Keytruda) elicited an overall response rate of 55.8% (95% CI, 45.7%-65.5%) in patients with metastatic clear cell RCC who received prior treatment with an immune checkpoint inhibitor. However, since these data stemmed from a single-arm trial, it is difficult to decipher whether these responses could be attributed to lenvatinib alone, or if pembrolizumab contributed to the benefit, Rini notes.

Two randomized trials are further addressing the use of immunotherapy in patients with RCC who have experienced disease progression on a prior checkpoint inhibitor, Rini continues. The phase 3 CONTACT-03 trial (NCT04338269) is evaluating cabozantinib (Cabometyx) plus atezolizumab (Tecentriq) vs cabozantinib alone in patients with advanced RCC who received prior treatment with a checkpoint inhibitor. This study has completed accrual in a refractory setting, and progression-free survival and overall survival data are expected to read out in the next year, Rini explains.

Additionally, the ongoing phase 3 TiNivo-2 trial (NCT04987203) is investigating the combination of tivozanib (Fotivda) plus nivolumab (Opdivo) vs tivozanib alone in patients with RCC who previously received 1 or 2 lines of therapy, including a checkpoint inhibitor. Notably, both trials included patients who progressed on adjuvant pembrolizumab, which is an emerging population within RCC, Rini says.

These 2 trials could help amplify the understanding of whether patients with RCC could benefit from immunotherapy after progression on a prior checkpoint inhibitor, and these results could affect how RCC is managed, Rini concludes.