The European Commission is reviewing data from the pivotal phase 3 CheckMate-9ER trial.
The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended approval of the combination of nivolumab (Opdivo) plus cabozantinib (Cabometyx) as a frontline treatment for patients with advanced renal cell carcinoma (RCC).1
The recommendation 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 European Commission will now review the CHMP recommendation and make a final decision in the next few months on whether to approve the combination.
“Today’s news is welcomed by physicians treating people living with advanced renal cell carcinoma,” sCristina Suárez, MD, medical oncologist at the Vall d´Hebron University Hospital, Barcelona, Spain, and a lead investigator on the CheckMate -9ER trial, stated in a press release. “The positive CHMP opinion brings us 1 step closer to the promise of a new approach that combines improved treatment outcomes, a favorable tolerability profile and superior health-related quality of life for patients.”
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. Ipsen Receives Positive CHMP Opinion Recommending Cabometyx® in Combination With Opdivo® as First-line Treatment for Patients Living With Advanced Renal Cell Carcinoma. Posted online February 26, 2021. Accessed February 26, 2021. https://bwnews.pr/3r0eZeB.
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.