First-line cabozantinib and nivolumab combination remains superior to sunitinib in kidney cancer treatment

Nivolumab plus cabozantinib maintains superiority over sunitinib with a durable survival benefit in untreated advanced renal cell carcinoma (RCC), according to long-term data presented at the 2025 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium (Abstract 439). The findings are based on an analysis of the final five years of the Phase 3 CheckMate 9ER clinical trial, which demonstrated the combination's durable progression-free survival (PFS), overall survival (OS) and objective response rate (ORR).

In these final results from the Checkmate 9ER trial, a long-term efficacy advantage of nivolumab plus cabozantinib over sunitinib was observed, with a median follow-up of 67.6 months. These results continue to support nivolumab plus cabozantinib as a standard treatment option for previously untreated advanced kidney cancer.

The study included651 patients with previously untreated renal cell carcinoma who were randomized 1:1 to receive 240 mg of nivolumab plus 40 mg of cabozantinib (once daily) or 50 mg of sunitinib (once daily) every 2 weeks for 4 weeks, 2 weeks. The trial's primary endpoint was PFS according to RECIST v1.1 criteria and was assessed by blinded independent central review. OS and ORR served as secondary endpoints.

After a median follow-up of 67.6 months, the combination maintained its clear PFS advantage over sunitinib, with a hazard ratio of 0.58 (95% confidence interval [CI], 0.49-0.70). The median PFS in the combination group was 16.4 months (95% CI, 12.5-19.3 months) compared with 8.3 months (95% CI, 7.0-9.7 months) in the sunitinib group. At 60 months, 13.6% of patients in the nivolumab plus cabozantinib group remained progression-free, compared with 3.6% in the sunitinib group. OS also favored the nivolumab combination group, with a hazard ratio of 0.79 (95% CI, 0.65-0.96). The median OS in the combination group was 46.5 months (95% CI, 40.6-53.8 months), while that in the sunitinib group was 35.5 months (95% CI, 29.2-42.8 months). The five-year overall survival rates were 40.9% and 35.4% respectively.

Combined medication groupThe ORR was 55.7% and 27.4% in the sunitinib group. The complete response rates were 13.9% and 4.6% respectively. In addition, 22.0% of responders in the combination arm maintained a response over 5 years, compared with 10.0% in the sunitinib arm. The most common grade 3-4 immune-related adverse events in the combination group occurred in 14% of patients, with thyroid abnormalities being the most common. Overall, 22% of participants received corticosteroids to treat any grade of immune-mediated adverse events. The researchers reported no new safety signals.

Long-term data confirm that immunotherapy-based regimens extend OS in first-line metastatic renal cell carcinoma, reaching a median survival of approximately 4 years. There is no doubt that dual immunotherapy prolongs overall survival in first-line patients.

References:https://www.oncologynewscentral.com/kidney-cancer/frontline-nivolumab-combination-maintains-superiority-over-sunitinib-in-kidney-cancer