Dr Choueiri on the Investigation of ICI Continuation in Advanced RCC

Author(s):

Toni Choueiri, MD, discusses remaining questions associated with the role of immune checkpoint inhibitor continuation following progression on a prior checkpoint blockade in advanced renal cell carcinoma, and attempts to address them through continued research.

Toni Choueiri, MD, medical director, International Strategic Initiatives, director, Lank Center for Genitourinary Oncology, co-leader, Kidney Cancer Program, senior physician, Dana-Farber Cancer Institute, Jerome and Nancy Kohlberg Chair and Professor of Medicine, Harvard Medical School, discusses remaining questions associated with the role of immune checkpoint inhibitor (ICI) continuation following progression on a prior checkpoint blockade in advanced renal cell carcinoma (RCC), and attempts to address them through continued research.

The potential benefit of re-challenge with an ICI regimen following progression on prior immune-based therapy has been under investigation in RCC. Accordingly, the phase 3 CONTACT-03 trial (NCT04338269) trial was designed to evaluate the addition of atezolizumab (Tecentriq) to cabozantinib (Cabometyx) for patients with metastatic RCC who have received a PD-1/PD-L1 inhibitor in the frontline.

Results from the trial were presented at the 2023 ASCO Annual Meeting, showing that patients with metastatic RCC treated with atezolizumab and cabozantinib did not experience improved clinical outcomes vs cabozantinib alone, Choueiri reports. Moreover, the combination regimen elicited a higher rate of toxicities. Overall, investigators concluded that the continued use of ICIs post-progression on a checkpoint blockade is not the superior treatment strategy in this setting.

Despite negative results, debate regarding the potential utility of re-challenge with immunotherapy combinations in advanced RCC is ongoing, Choueiri says. More phase 3 evidence is required before a definitive statement can be made in support of or against this approach, he adds.

The ongoing, phase 3 TiNivo-2 trial (NCT04987203) is another attempt to address the question of immunotherapy continuation in patients with advanced RCC, Choueiri continues. Patients enrolled onto this trial will either continue ICI therapy with nivolumab (Opdivo) plus the TKI tivozanib (Fotivda) or discontinue immunotherapy and switch to tivozanib monotherapy. To enroll, patients must have progressed following 1 to 2 lines of therapy, including an ICI, and have experienced disease progression during or following at least 6 weeks of ICI treatment in either the first or second line.