The European Commission has approved the combination of nivolumab (Opdivo) and cabozantinib (Cabometyx) as a frontline treatment for patients with advanced renal cell carcinoma (RCC).1
The approval was 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).
"The combination of nivolumab and cabozantinib pairs two proven agents for advanced renal cell carcinoma that together have shown superior efficacy across key endpoints and subgroups of patients compared to sunitinib in the CheckMate-9ER trial. Additionally, the combination’s safety profile was manageable with known protocols, leading to a low rate of treatment-related discontinuations,” Marc-Oliver Grimm, MD, professor of Medicine and Urology Department Head, Jena University Hospital, Germany, stated in a press release.
“With today’s approval, clinicians in the EU will be able to offer patients with advanced renal cell carcinoma an additional combination therapy that may help them achieve early control of their disease and improve survival outcomes,” added Grimm.
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.
In the United States nivolumab/cabozantinib was approved by the FDA on January 22, 2021, as a frontline treatment for patients with advanced RCC.
1. European Commission approves Cabometyx® in combination with Opdivo® as a first-line treatment for patients living with advanced renal cell carcinoma. Posted online March 31, 2021. Accessed March 31, 2021. https://bit.ly/31AKocs.
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.