According to long-term follow-up data from the phase 3 CheckMate-214 trial, nivolumab plus ipilimumab demonstrated long-term survival and more durable response compared to sunitinib among patients with advanced clear cell renal cell carcinoma. 

These results were first presented by Nizar M. Tannir, MD, MD Anderson Cancer Center at University of Texas, Houston, at the 2024 American Society for Clinical Oncology (ASCO) Genitourinary Cancers Symposium.

As previously reported, “first-line [nivolumab plus ipilimumab] has provided substantial long-term survival benefits over [sunitinib]”, stated Dr Tannir and coauthors. Here, study investigators “report survival, response per independent radiology review committee and safety” after 6-years median follow up. 

In this open-label study, patients were randomized on a 1-to-1 basis to receive either 3 mg/kg of nivolumab plus 1 mg/kg of ipilimumab once every 3 weeks (maximum of 4 doses), followed by 3 mg/kg of nivolumab every 2 weeks; or 50 mg of daily sunitinib (4 weeks on and 2 weeks off). Primary end points included overall-survival (OS), progression-free survival (PFS), and objective response rate (ORR) among patients with IMDC intermediate/poor risk (IP) disease (n = 847). Secondary end points included OS, PFS, and ORR among patients in the intention-to-treat (ITT) population (n = 1,096) and patients with favorable risk (n = 249). Exploratory outcomes in long-term survivors were assessed post hoc. 

In the IP population, median OS was 47 months in the nivolumab plus ipilimumab arm (hazard ratio HR 0.68) and 26 months in the sunitinib arm. Median PFS was 11 months ([HR] 0.73) in the nivolumab plus ipilimumab arm and 8 months in the sunitinib arm. ORR was 42% in the nivolumab plus ipilimumab arm and 27% in the sunitinib arm and complete response (CR) was 11% and 2%, respectively. Median DOR was 75 months in the nivolumab plus ipilimumab arm and 20 months in the sunitinib arm.

In the ITT population, median OS was 53 months in the nivolumab plus ipilimumab arm (HR 0.72) and 37 months in the sunitinib arm, with a median PFS of 12 months in both treatment arms. ORR was 39% in the nivolumab plus ipilimumab arm and 32% in the sunitinib arm and CR was 12% and 3%, respectively. Median DOR was 75 months in the nivolumab plus ipilimumab arm and 25 months in the sunitinib arm.

In the favorable risk population, median OS was 79 months in the nivolumab plus ipilimumab arm (HR 0.87) and 68 months in the sunitinib arm. Median PFS was 12 months in the nivolumab plus ipilimumab arm (HR 1.60) and 29 months in the sunitinib arm. ORR was 30% in the nivolumab plus ipilimumab arm and 52% in the sunitinib arm and CR was 13% and 6%, respectively. Median DOR was 61 months in the nivolumab plus ipilimumab arm and 33 months in the sunitinib arm.

Incidence of any grade 3/4 treatment-related adverse events remained largely unchanged. However, 1 additional drug-related death occurred in the nivolumab plus ipilimumab arm. 

At post hoc analysis, ORR was 66% in the nivolumab plus ipilimumab arm and 53% in the sunitinib arm and CR was 27% and 9%, respectively. In the nivolumab plus ipilimumab arm 4% of patients experienced disease progression compared with 11% of patients in the sunitinib arm. Medan DOR was 76 months in the nivolumab plus ipilimumab arm and 40 months in the sunitinib arm.

“[Nivolumab plus ipilimumab] demonstrated long-term survival and more durable response benefits,” concluded Dr Tannir and coauthors. “CR rates were higher and median DOR was longer with [nivolumab plus ipilimumab vs sunitinib] regardless of IMDC risk group, and in LTS pts.”

Source: 

Tannir NM, Escudier B, McDermott DF, et al. Nivolumab plus ipilimumab (NIVO+IPI) vs sunitinib (SUN) for first-line treatment of advanced renal cell carcinoma (aRCC): Long-term follow-up data from the phase 3 CheckMate 214 trial. Presented at the 2024 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium in San Francisco, California. Abstract 363