In the study, researchers conducted a large randomized phase 3 trial to explain combination immunotherapy could be a new standard of care for some patients with advanced renal cell carcinoma (RCC)

In the trial, both overall survival and objective response rates were significantly higher with nivolumab plus ipilimumab as compared to sunitinib in patients with intermediate- and poor-risk advanced RCC.

"The study showed improvement in response and overall survival compared to sunitinib for patients with intermediate or poor features, comprising about 80% of patients with metastatic RCC," said lead author Robert Motzer.

The combination of nivolumab plus ipilimumab has already been investigated in several tumor types, and response rates tend to be better than those of either agent used alone. The combination has been approved for the treatment of advanced melanoma.

The combination has also demonstrated antitumor activity in untreated and previously treated patients with advanced RCC, the authors note.

The cohort included 1082 patients with previously untreated clear-cell advanced RCC who were randomly assigned to receive treatment with nivolumab plus ipilimumab or with sunitinib. In the intent-to-treat population, 423 patients had the intermediate-risk disease, and 416 patients had the poor-risk disease.

The co-primary endpoints were overall survival, objective response rate, and progression-free survival in the group at intermediate or reduced risk.

In the intermediate- and poor-risk group, the 12-month overall survival rate was significantly better in the nivolumab plus ipilimumab arm compared with that in the sunitinib arm: 80% vs. 72%. The median overall survival was not reached with nivolumab plus ipilimumab. It was 26.0 months with sunitinib.

For progression-free survival, the median was 11.6 months with nivolumab plus ipilimumab and 8.4 months with sunitinib, but the difference between groups did not meet the prespecified threshold for statistical significance.

The authors assessed outcomes for the entire intent-to-treat population. The 12-month overall survival rate was 83% for immunotherapy vs. 77% with sunitinib; the 18-month overall survival rate was 78% vs. 68%.

The median overall survival did not reach for the nivolumab plus ipilimumab arm; it was 32.9 months for the sunitinib arm. The rate of independently assessed objective response was 39% with nivolumab plus ipilimumab and 32% with sunitinib.

Median progression-free survival rates were similar for both groups: 12.4 with nivolumab plus ipilimumab and 12.3 months with sunitinib. The 12-month overall survival rate was 94% with nivolumab plus ipilimumab and 96% with sunitinib. The 18-month overall survival rates were 88% and 93%, respectively.

The objective response rate was 29% with nivolumab plus ipilimumab vs. 52% with sunitinib (< .001). The median progression-free survival was 15.3 months vs 25.1 months (hazard ratio for disease progression or death, 2.18; 99.1% CI, 1.29 – 3.68; < .001), favoring sunitinib. The rate of complete response, however, was 11% with nivolumab plus ipilimumab and 6% with sunitinib.

Patients who received the immunotherapy combination had fewer grade 3-4 adverse events than those who received sunitinib (46% vs. 63%), but there were more discontinuations (22% with immunotherapy vs. 12% with sunitinib) and more treatment-related deaths.

Overall, treatment-related adverse events of any grade occurred in 93% of patients in the immunotherapy group vs. 97% of those treated with sunitinib.