Dr Tsao on the Investigation of Cabozantinib With Nivolumab and Ipilimumab in RCC

Che-Kai Tsao, MD, associate professor of medicine, Hematology and Medical Oncology, the Icahn School of Medicine at Mount Sinai, discusses the investigation of cabozantinib (Cabometyx) in combination with nivolumab (Opdivo) and ipilimumab (Yervoy) in patients with renal cell carcinoma (RCC).

The phase 3 COSMIC-313 trial (NCT03937219) was a multicenter, randomized, double-blinded, placebo-controlled trial that evaluated cabozantinib or placebo plus nivolumab and ipilimumab in previously untreated patients with advanced or metastatic RCC. The study accrued patients who had intermediate- or poor-risk advanced RCC, Tsao says, adding that the majority of patients had intermediate-risk disease.

Data presented at the 2023 Genitourinary Cancers Symposium showed that the triplet elicited a progression-free survival (PFS) benefit over the doublet plus placebo. In the intent-to-treat population, the median PFS was 16.9 months (95% CI, 11.5–not estimable [NE]) for the cabozantinib group vs 11.3 months (95% CI, 7.7-14.0) for the placebo group (HR, 0.74; 95% CI, 0.58-0.94). However, the overall survival (OS) results were not yet mature, Tsao says.

The overall response rates (ORRs) were below 50% for both the intermediate- and poor-risk populations, which was disappointing, Tsao says. For the intermediate-risk subgroup, the cabozantinib regimen produced an ORR of 45%, compared with 36% for the placebo regimen. For the poor-risk subgroup, the ORRs were 36% and 38% for the cabozantinib and placebo arms, respectively.

Tsao also explains that a notable proportion of patients were not able to complete the 4 cycles of nivolumab and ipilimumab, despite this specific portion of treatment being important. It remains to be seen if the triplet combination of cabozantinib, nivolumab, and ipilimumab will eventually be approved by the FDA for first-line use, Tsao says. Additionally, in a recent presentation, Thomas Powles, MD, of Barts Cancer Centre, presented data from a subgroup analysis that showed patients who have benefited the most from treatment are those with intermediate high-risk disease. Therefore, investigators will aim to better understand which patients could benefit most from this triplet approach, Tsao concludes.