New analyses from the phase III CheckMate 9ER trial are being presented at the 2021 Genitourinary Cancers Symposium. These new findings demonstrate clinically meaningful, sustained efficacy benefits as well as quality-of-life improvements with the combination of nivolumab and cabozantinib compared to sunitinib in the first-line treatment of advanced renal cell carcinoma (RCC).
Extended Follow-up and Outcomes by Sarcomatoid Histology
With a median follow-up of 23.5 months, nivolumab in combination with cabozantinib continued to show superior progression-free survival, objective response rates, and overall survival vs sunitinib, with a low rate of treatment-related adverse events leading to discontinuation. No new safety signals were identified with extended follow-up, according to an abstract by Motzer et al (Abstract 308).
Across the full study population:
- The combination doubled median progression-free survival (17.0 months vs 8.3 months, respectively; hazard ratio [HR] = 0.52, 95% confidence interval [CI] = 0.43–0.64), the trial’s primary endpoint, compared to sunitinib
- Nearly twice as many patients responded to nivolumab plus cabozantinib vs sunitinib (54.8% vs 28.4%)
- Nivolumab plus cabozantinib maintained improvements in overall survival, demonstrating a 34% reduction in the risk of death compared to sunitinib (HR = 0.66, 95% CI = 0.50–0.87)
- In an exploratory analysis, the combination was associated with a disease control rate (including complete response, partial response, and stable disease) of 88.2% vs 69.9% with sunitinib
- The complete response rate, also exploratory, for the combination was 9.3% compared to 4.3% with sunitinib
- Among patients treated with nivolumab plus cabozantinib, 6.6% discontinued both agents due to treatment-related adverse events; 9.7% discontinued nivolumab only and 7.2% discontinued cabozantinib only.
In an exploratory subgroup analysis of 75 patients with sarcomatoid features, the combination showed benefit in this population typically associated with a poor prognosis, reducing the risk of death by 64% vs sunitinib (HR = 0.36, 95% CI = 0.17–0.79) and demonstrating both superior progression-free survival (10.3 months vs 4.2 months) and objective response rate (55.9% vs 22.0%).
Patient-Reported Outcomes
In a separate analysis from the CheckMate 9ER trial conducted with 18.1 months of median follow-up, patients treated with the combination of nivolumab and cabozantinib reported statistically significant health-related quality-of-life benefits (Abstract 285). Treatment with nivolumab in combination with cabozantinib was associated with a lower treatment burden, decreased risk of deterioration, and a reduction of disease-related symptoms compared to sunitinib. These exploratory outcomes were measured using Functional Assessment of Cancer Therapy Kidney Symptom Index-19 (FKSI-19), a quality-of-life tool specific to kidney cancer, and EQ-5D-3L instruments.
Robert Motzer, MD
“There is a continued need for new therapies that show benefit across subgroups of patients with advanced renal cell carcinoma,” said Robert Motzer, MD, Kidney Cancer Section Head, Genitourinary Oncology Service, and Jack and Dorothy Byrne Chair in Clinical Oncology at Memorial Sloan Kettering Cancer Center. “In CheckMate 9ER, nivolumab in combination with cabozantinib doubled progression-free survival, increased overall survival and response rate and, in an exploratory analysis, showed impressive disease control, and these promising efficacy results were sustained with extended follow-up…of note, patients in this study reported significant quality-of-life improvements, which are important for patients undergoing treatment for this challenging disease.”
Nivolumab plus cabozanitinib was approved for the first-line treatment of advanced renal cell carcinoma by the U.S. Food and Drug Administration (FDA) in January 2021, and further applications are under review with health authorities globally.
Disclosures: For full disclosures of the study authors, visit coi.asco.org (Abstract 308 and Abstract 285).
