The approval is based on data from the phase 3 CheckMate-9ER trial.
The FDA has approved the combination regimen of nivolumab (Opdivo) plus cabozantinib (Cabometyx) as a frontline treatment for patients with advanced renal cell carcinoma (RCC).1
The approval is based on findings from the phase 3 CheckMate-9ER trial (NCT03141177). Study results showed that the combination reduced the risk of disease progression or death by 49% versus sunitinib (Sutent) in treatment-naïve patients with advanced RCC, with a median progression-free survival of 16.6 months versus 8.3 months, respectively (HR, 0.51; P <.0001).2
Additional findings showed that, at a median follow-up of 18.1 months, the median overall survival was not reached in either arm, and there was a 40% reduction in the risk of death with the combination (HR, 0.60; P = .001).
“This combination of cabozantinib and nivolumab significantly improved key efficacy measures compared to sunitinib—progression-free survival, overall survival, and objective response rate—while showing a low rate of treatment discontinuations due to side effects. The therapeutic benefit demonstrated in CheckMate -9ER and quality of life measures explored emphasize the role of this combination for patients with advanced kidney cancer,” Toni Choueiri, MD, director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute and the Jerome and Nancy Kohlberg Professor of Medicine at Harvard Medical School, stated in a press release. “With this important FDA approval, the combination is poised to become a standard in newly diagnosed metastatic kidney cancer.”
In the international, randomized, phase 3 CheckMate-9ER trial, 651 patients with advanced RCC received the combination of nivolumab and cabozantinib (n = 323) or sunitinib (n = 328) in the first-line setting. Patients must have had previously untreated advanced or metastatic disease, a clear cell component, and any International Metastatic RCC Database Consortium (IMDC) risk score.
The combination demonstrated a benefit across numerous subgroups, including age, sex, PD-L1 expression, bone metastases, IMDC risk group, and geographic region.
The objective response rate (ORR) was also doubled with nivolumab/cabozantinib in this setting compared with sunitinib, at 55.7% versus 27.1%, respectively (P <.0001). In the combination arm, the complete response (CR) rate was 8.0%, the partial response (PR) rate was 47.7%, and the stable disease (SD) rate was 32.2%. Additionally, 5.6% of patients had progressive disease (PD) and 6.5% were not evaluable or not assessed. In the sunitinib arm, the CR, PR, and SD rates were 4.6%, 22.6%, and 42.1%, respectively. Moreover, 13.7% of patients had PD and 17.1% of patients were not evaluable or not assessed.
Regarding safety, the incidence of the most common, any-grade and high-grade treatment-related adverse events (TRAEs) were similar in both arms. More than 50% of patients on the combination required dose reductions of cabozantinib due to adverse effects (AEs). TRAEs led to treatment discontinuations in 15.3% of those in the nivolumab/cabozantinib arm and in 8.8% of those on sunitinib. Specifically, 3.1% of patients discontinued both nivolumab and cabozantinib due to AEs, 5.6% discontinued only nivolumab, and 6.6% discontinued only cabozantinib.
The overall rate of serious AEs was similar between the 2 groups; however, liver toxicity was more common with cabozantinib/nivolumab. Nineteen percent of patients on the combination required corticosteroids due to immune-related AEs, 4% of whom needed corticosteroids for at least 30 days.
Cabozantinib was approved by the FDA in December 2017 for use in previously untreated patients with advanced RCC. The FDA approved nivolumab in November 2015 for use in patients with metastatic RCC who progressed on an angiogenesis inhibitor. Nivolumab also has an FDA-approved RCC indication in the frontline setting for use in combination with ipilimumab (Yervoy) as a treatment for intermediate- and poor-risk patients with advanced disease.
1. Exelixis Announces U.S. FDA Approval of CABOMETYX® (cabozantinib) in Combination with OPDIVO® (nivolumab) as a First-Line Treatment for Patients with Advanced Renal Cell Carcinoma. Published online January 22, 2021. Accessed January 22, 2021. https://bwnews.pr/3c2w2bf.
2. Choueiri TK, Powles T, Burotto M, et al. Nivolumab + cabozantinib vs sunitinib in first-line treatment for advanced renal cell carcinoma: first results from the randomized phase 3 CheckMate 9ER trial. Ann Oncol. 2020;31(4). Abstract 696O.