As reported in The Lancet Oncology by Robert J. Motzer, MD, and colleagues, the protocol-defined final overall survival analysis of the phase III CheckMate 9ER trial showed a significant benefit with nivolumab/cabozantinib vs sunitinib in previously untreated patients with advanced renal cell carcinoma (RCC).
The primary analysis of the trial showed that nivolumab/cabozantinib was associated with superior progression-free survival, the primary endpoint, as well as improved overall survival and objective response rate vs sunitinib at a median follow-up of 18.1 months. The primary analysis supported the January 2021 approval of nivolumab/cabozantinib in this setting.
Robert J. Motzer, MD
In the open-label trial, 651 patients from sites in 18 countries were randomly assigned between September 2017 and May 2019 to receive nivolumab at 240 mg every 2 weeks plus cabozantinib at 40 mg once daily (n = 323) or sunitinib at 50 mg once daily for 4 weeks in 6-week cycles. Overall survival was a secondary endpoint.
Key Findings
After a median follow-up of 32.9 months (interquartile range = 30.4–35.9 months), median overall survival was 37.7 months (95% confidence interval [CI] = 35.5 months–not estimable) in the nivolumab/cabozantinib group vs 34.3 months (95% CI = 29.0 months–not estimable) in the sunitinib group (hazard ratio [HR] = 0.70, 95% CI = 0.55–0.90, P = .0043). Rates at 24 months were 70% vs 60%. The updated median progression-free survival was 16.6 months (95% CI = 12.8–19.8 months) in the nivolumab/cabozantinib group vs 8.3 months (95% CI = 7.0–9.7 months) in the sunitinib group (HR = 0.56, 95% CI = 0.46–0.68, P < .0001), with 24-month rates of 39.5% vs 20.9%.
A total of 228 patients (71%) in the nivolumab/cabozantinib group and 274 (86%) in the sunitinib group had discontinued study treatment at the time of analysis, with the most common reason being disease progression in both groups. Among patients who discontinued treatment, 31% in the nivolumab/cabozantinib group and 45% in the sunitinib group received subsequent systemic therapy; the most common treatments were a VEGF- or VEGFR-targeted agent in the nivolumab/cabozantinib group (27%) and a nivolumab-based or other PD-1 or PD-L1 inhibitor–based therapy in the sunitinib group (34%).
KEY POINTS
- After a median follow-up of 32.9 months, median overall survival was 37.7 months in the nivolumab/cabozantinib group vs 34.3 months in the sunitinib group. Rates at 24 months were 70% vs 60%.
- Updated median progression-free survival was 16.6 months in the nivolumab/cabozantinib group vs 8.3 months in the sunitinib group, with 24-month rates of 39.5% vs 20.9%.
In the updated analysis, grade 3 or 4 treatment-related adverse events occurred in 65% of patients in the nivolumab/cabozantinib group vs 54% of the sunitinib group, most commonly hypertension (13% vs 12%), palmar-plantar erythrodysesthesia (8% vs 8%), and diarrhea (7% vs 5%). Grade 3 or 4 treatment-related serious adverse events occurred in 22% vs 10% of patients. Since the primary analysis, one new treatment-related death was observed, due to sudden death in a patient in the sunitinib group.
The investigators concluded, “With extended follow-up and preplanned final overall survival analysis per protocol, nivolumab plus cabozantinib demonstrated improved efficacy vs sunitinib, further supporting the combination in the first-line treatment of advanced renal cell carcinoma.”
Dr. Motzer, of the Department of Medicine, Memorial Sloan Kettering Cancer Center, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Bristol Myers Squibb and Ono Pharmaceutical. For full disclosures of the study authors, visit thelancet.com.
