Dr Albigès on Survival Outcomes With Cabozantinib Plus Nivolumab and Ipilimumab in RCC

“With more follow-up, we see a sustained benefit in PFS favoring the triplet. …Unfortunately, there was no differences in terms of OS between the two treatment arms.”

Laurence Albigès, MD, PhD, medical oncologist, head, Department of Oncology, Institut Gustave Roussy, Paris, discusses final overall survival (OS) data and exploratory analyses from the phase 3 COSMIC-313 trial (NCT03937219) evaluating the triplet combination of cabozantinib (Cabomety) plus nivolumab (Opdivo) and ipilimumab (Yervoy) in patients with intermediate- or poor-risk advanced renal cell carcinoma (RCC).

At 45 months of follow-up, the final analysis of COSMIC-313 was presented during the 2025 Genitourinary Cancers Symposium, and demonstrated a sustained progression-free survival (PFS) benefit with cabozantinib plus nivolumab and ipilimumab vs nivolumab and ipilimumab alone, Albiges reports. PFS increased from 11.2 months (95% CI, 9.3-14.0) with nivolumab plus ipilimumab plus placebo to 16.6 months (95% CI, 14.0-22.6) with the triplet, with the benefit primarily observed in patients with International Metastatic RCC Database Consortium intermediate-risk disease (n = 75), she states.

Despite the improvement in PFS, overall survival (OS) outcomes did not differ significantly between the triplet and doublet arms in this final analysis, Albiges notes. The safety profile remained consistent with prior reports, reinforcing the challenges of administering a triplet regimen in a blinded trial setting, Albiges adds.

This final analysis also included the first biomarker analysis from the trial, which utilized RNA sequencing (RNA-seq) data to explore molecular correlates of response, Albiges continues. Two approaches were used: molecular clustering and a deconvolution model to assess immune cell populations. The molecular clustering analysis, based on the framework established in the IMmotion program, identified seven molecular clusters; however, these were not specifically associated with the benefit of the triplet regimen, she notes.

In the deconvolution model, the relative abundance of immune cell populations was estimated. Notably, a population of M2-like macrophages was identified as a biomarker associated with worse prognosis in patients receiving the doublet, Albiges details. The addition of cabozantinib in the triplet regimen appeared to mitigate this poor prognosis, suggesting that patients with high M2-like macrophage expression may derive greater benefit from the inclusion of a TKI into treatment, she says. This finding is hypothesis-generating and requires further prospective validation, Albiges concludes.