Dr Tsao on the Role of Nivolumab Plus Cabozantinib in Advanced RCC

Che-Kai Tsao, MD, associate professor of medicine, hematology and medical oncology, the Icahn School of Medicine at Mount Sinai, discusses key updates from the phase 3 CheckMate 9ER trial (NCT03141177), and how these data clarify the role of nivolumab (Opdivo) plus cabozantinib (Cabometyx) as a new standard of care (SOC) in renal cell carcinoma (RCC).

The randomized CheckMate 9ER trial randomly assigned previously untreated patients with advanced or metastatic RCC to recieve nivolumab and cabozantinib vs sunitinib (Sutent), Tsao begins. Prior data from this trial demonstrated that the combination led to an improvement in both progression-free survival (PFS) and overall survival (OS), he states.

Updated findings from this trial were presented at the 2023 Genitourinary Cancers Symposium, Tsao continues. At a minimum of 33 months follow-up, patients in the overall population who received the nivolumab and cabozantinib doublet continued to demonstrate a strong PFS and OS benefit vs those given sunitinib, Tsao reports. Hazard ratios for the doublet were 1.07 in the favorable-risk group, 0.75 in the intermediate-risk group, 0.46 in the poor risk group, and 0.65 in the intermediate-/poor-risk group, respectively.

When patients were analyzed according to risk status, those in the favorable risk group may not have achieved the degree of OS benefit expected, Tsao notes. Additionally, median OS in the combination arm of the favorable risk subgroup was not reached, while median OS in the control arm was 47.6 months, Tsao adds. In the overall population, median OS improved by 11.8 months with the doublet.

Additional efficacy results showed that the overall response rate (ORR) continued to benefit with the combination across subgroups. In the favorable risk group, the ORR was 66% with the doublet vs 44% with sunitinib. These ORRs were comprised of 14% and 11% complete responses, respectively. Moreover, an exploratory post-hoc analysis of this trial showed that patients experienced a PFS and OS benefit with the regimen independent of PD-L1 and c-MET tumor status.

Based on results from CheckMate 9ER, the combination of nivolumab and cabozantinib was approved by the FDA for for the treatment of this patient population in January 2021. Ultimately, these updated data confirm the long-term efficacy of nivolumab plus cabozantinib and support its new role as a SOC in the frontline setting for metastatic RCC, Tsao concludes.