Nivolumab Plus Ipilimumab Yields Long-Lasting Benefit Vs Sunitinib in Advanced Renal Cell Carcinoma

A durable clinical benefit was observed following treatment with nivolumab (Opdivo) and ipilimumab (Yervoy) vs sunitinib (Sutent) in patients with advanced renal cell carcinoma, according to the 5-year follow-up findings of the phase 3 CheckMate 214 study (NCT02231749).

At the median follow-up of 67.7 months, the median overall survival (OS) was 55.7 months vs 38.4 months (HR, 0.72; 95% CI, 0.62-0.85) in the combination and single-agent groups, respectively. For patients who were intermediate-risk or poor-risk, the median was 47.0 months vs 26.6 months (HR, 0.68; 95% CI, 0.58-0.81) in the nivolumab and sunitinib groups, respectively. Favorable risk patients had a median OS of 74.1 months vs 68.4 months in the across both respective groups.

The median progression-free survival (PFS) was 12.3 months vs 12.3 months (HR, 0.86; 95% CI, 0.73-1.01; P = .0628) in the experimental and control arms, respectively. The 5-year PFS probability in each population was 30.0% vs 14.0% in the intent-to-treat (ITT) population across both respective groups, and 31.0% vs 11.0% in the intermediate-risk/poor-risk group. However, for those with favorable-risk disease, the HR favored sunitinib with regard to PFS (HR, 1.60; 95% CI, 1.13-2.26), but the 5-year PFS probability was 26% vs 21% in the nivolumab and sunitinib groups, respectively.

A total of 1096 patients were enrolled on the trial. The nivolumab plus ipilimumab group included 550 patients in the ITT population, 425 of whom were intermediate /poor risk, and 125 were favorable risk. A total of 546 patients in the ITT sunitinib group, 422 of whom were intermediate risk/poor risk and 124 were favorable risk. Additionally, 547 patients in the nivolumab group and 535 in the sunitinib group were included in the safety analysis. At the 5-year follow-up, 34 patients in the nivolumab group and 9 in the sunitinib group were still on treatment.

The median duration of therapy was 7.9 months vs 7.8 months. Moreover, 305 patients in the nivolumab group and 372 patients in the sunitinib group received a subsequent therapy.

The objective response rate (ORR) was 39.3% vs 32.4% in the nivolumab plus ipilimumab and sunitinib groups, respectively. The ORR in the intermediate-risk/poor-risk group was 42.0% for those receiving nivolumab and 27.0% for those receiving sunitinib group. For those with favorable-risk disease, the ORR in the nivolumab group was 30% vs 52% in the sunitinib group; the complete response (CR) rate was 12% vs 3% in the ITT population, 11% vs 2% in the intermediate-risk/poor-risk group, and 13% vs 6% in the favorable-risk group. A total of 9.6% of patients in the nivolumab group and 2.4% in the sunitinib group achieved a CR.

In the nivolumab group, 18 patients discontinued treatment vs 7 in the sunitinib group. Additionally, the median duration of study therapy in the nivolumab group was 32.8 months and 7.8 months in the sunitinib group.

The median time to response 2.8 months vs 4.0 months across both respective groups. The duration of response was not reached in the combination arm vs 24.8 month in the single-agent arm. Treatment-free interval was assessed in more ITT responders without subsequent therapy in 48% of patients in the nivolumab group and 24% in the sunitinib group.

Grade 3/4 treatment-related adverse effects (TRAEs) occurred in 48% of patients in the nivolumab group and 64% in the sunitinib group. Moreover, 23% vs 13% of TRAEs lead to discontinuation. Additionally, 162 patients in the nivolumab group received 40 mg or more of prednisone daily with 108 patients receiving it continuously; 56 received it continously for 30 days or more.

Reference

Motzer RJ, McDermott DF, Escudier B, et al. Conditional survival and long-term efficacy with nivolumab plus ipilimumab versus sunitinib in patients with advanced renal cell carcinoma. Cancer. Published Online April 5, 2022. doi:10.1002/cncr.34180