Dr Choueiri on the Results of the CONTACT-03 Trial in Metastatic RCC

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 the results of the phase 3 CONTACT-03 trial (NCT04338269) of atezolizumab (Tecentriq) and cabozantinib (Cabometyx) in patients with metastatic renal cell carcinoma (RCC).

Immune checkpoint inhibitors are sometimes used in patients following progression on prior checkpoint inhibition, Choueiri begins. However, this approach has not been tested nor approved, leaving few effective options available for the treatment of patients who progress on frontline immune-based combination therapy. Currently, the VEGF TKI cabozantinib is used in the second-line setting in patients who have been previously treated with immune-based therapy. It was unknown whether patients could derive benefit from the continuation ofimmune checkpoint inhibition, Choueiri says. To address this, investigators conducted a phase 3 trial in patients post-progression on PD-1/PD-L1 inhibitors.

In the phase 3 trial, 522 patients were randomly assigned to receive 60 mg of cabozantinib once a day orcabozantinib plus 1200 mg of the PD-L1 inhibitor atezolizumab once every 3 weeks, Choueiri continues. The primary end point of the study was independent centrally-assessed progression-free survival. The median PFS in the combination arm (n = 263) was 10.6 months (95% CI, 9.8-12.3) compared with 10.8 months (95% CI, 10.0-12.5) with cabozantinib alone (n = 259), failing to meet the primary end point of the study. Additionally, median overall survival, a key secondary end point of the trial, was 25.7 months (95% CI, 25.1-not evaluable) with the combination and was not evaluable with cabozantinib alone (95% CI, 21.1-NE). Overall, the addition of atezolizumab to cabozantinib did not improve clinical outcomes in this patient population, Choueiri notes.

Notably, toxicity was higher with the combination of cabozantinib and atezolizumab, Choueiri says. Taken collectively, the results indicate that the use of immune checkpoint inhibitors following progression on prior checkpoint blockade should not be standard of care in this setting, Choueiri concludes.