The combination of nivolumab and ipilimumab improved overall survival (OS) over sunitinib in patients with previously untreated advanced or metastatic renal cell carcinoma (RCC), according to results of the CheckMate 214 trial presented at the ESMO 2017 Congress (abstract LBA 5).

The phase 3, randomized, open-label trial was stopped early after it met one of its primary end points: improved OS with nivolumab (Opdivo, Bristol-Myers Squibb) and ipilimumab (Yervoy, Bristol-Myers Squibb) compared with sunitinib (Sutent, Pfizer) in intermediate- and poor-risk patients. The investigators reported that the combination had a significant OS benefit, reducing the risk of death in that higher-risk population by 37%.

The CheckMate 214 investigators, led by Bernard Escudier, MD, from the Institut Gustave Roussy, in Villejuif, France, evaluated 1,096 patients with previously untreated advanced or metastatic RCC. Patients were randomly assigned to receive nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg) every three weeks for four doses, then nivolumab (3 mg/kg) every two weeks (n=550), or sunitinib (50 mg once daily) for four weeks on and two weeks off (n=546). The patients in both arms were treated until progression or unacceptable toxicity.

Among the 847 patients with intermediate- or poor-risk disease, the combination resulted in a significantly better overall response rate than sunitinib (42% vs. 27%, respectively), “with a 9.4% complete response rate and durable responses.” There was a trend toward improved progression-free survival (PFS) in that population (hazard ratio [HR], 0.82; 95% CI, 0.64-1.05; P=0.0331), but it did not reach the prespecified significance threshold (P=0.009). Median PFS was 11.6 months with the combination and 8.4 months with sunitinib.

The combination improved OS in the intermediate-/poor-risk group, with the median OS not reached in the combination group, versus 26 months in the sunitinib group (HR, 0.63; P<0.0001). The combination also resulted in improved OS in the intention-to-treat population, a secondary end point of the trial (OS, not reached in the combination group vs. 32.9 months in the sunitinib group; HR, 0.68; P=0.0003).

The investigators considered the adverse event (AE) profile of the combination “manageable and consistent with previous studies.” Grade 3 to 5 AEs occurred in 46% of the patients treated with the combination and 63% of those treated with sunitinib.

They concluded that their data “support the use” of the nivolumab-ipilimumab combination in the first-line treatment of patients with advanced RCC.

 

—Sarah Tilyou