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.
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%).
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.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.