Nivolumab plus ipilimumab superior to sunitinib in advanced renal cell carcinoma

First-line treatment with nivolumab plus ipilimumab (NIVO+IPI) results in better survival and response benefits in patients with advanced renal cell carcinoma (aRCC) when compared with sunitinib (SUN), as shown by long-term follow-up data from the CheckMate 214 trial.

In addition, patients treated with NIVO+IPI have higher complete response (CR) rates and longer median duration of response (DOR) than those who received SUN, regardless of the International Metastatic RCC Database Consortium (IMDC) risk group. NIVO+IPI also has a favourable safety profile.

“First-line NIVO+IPI has provided substantial long-term survival benefits over SUN in patients with aRCC in CheckMate 214,” according to first author Nizar M Tannir, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, US.

“We report survival, response per independent radiology review committee (IRRC), and safety after 6 years minimum (median 80 months) follow-up in all randomized patients, by IMDC risk and in patients with overall survival (OS) ≥6 years (long-term survivors; LTS). Longer follow-up data (minimum, 7.5 years) will be presented,” Tannir said.

In this phase III trial, patients with aRCC were randomly assigned in a 1:1 ratio to receive either NIVO 3 mg/kg plus IPI 1 mg/kg Q3W34 then NIVO 3 mg/kg Q2W or SUN 50 mg QD for 4 weeks on, 2 weeks off.

Tannir and colleagues assessed OS, progression-free survival (PFS), objective response rate (ORR; both per IRRC using RECIST v1.1) in IMDC intermediate/poor risk (IP; primary), intent-to-treat (IRR; secondary), and favourable risk (exploratory) patients. They also performed a post hoc evaluation of the exploratory outcomes in LTS patients.

Long-term survival

Compared with SUN, treatment with NIVO+IPI demonstrated superior OS in both ITT (hazard ratio [HR], 0.72, 95 percent confidence interval [CI], 0.62‒0.83) and IP (HR, 0.68, 95 percent CI, 0.58‒0.81) patients. However, OS benefits did not differ significantly between the two arms among patients with a favourable risk (HR, 0.87, 95 percent CI, 0.62‒1.24). [ASCO GU 2024, abstract 363]

“Median PFS was consistent with previous reports,” according to the researchers.

NIVO+IPI also resulted in higher ORR per IRRC as compared with SUN, with more ongoing responses in ITT (60 percent vs 50 percent) and IP (60 percent vs 50 percent) patients. On the other hand, favourable risk patients had lower ORR with NIVO+IPI than with SUN, but more response were ongoing (59 percent vs 52 percent).

Regardless of IMDC risk, median DOR was longer and CR rate was higher in the NIVO+IPI group than in the SUN group.

No significant changes were observed in the incidence of any and grade 3‒4 treatment-related adverse events. However, one additional drug-related death occurred with NIVO+IPI and none with SUN since the previous database lock, according to the researchers.

In the LTS subgroup (NIVO+IPI: n=208; SUN: n=151), ORR (66 percent vs 53 percent) and CR (27 percent vs 9 percent) rates were higher and fewer patients had disease progression (4 percent vs 11 percent) with NIVO+IPI than with SUN. Additionally, median DOR was longer with NIVO+IPI (n=137) than with SUN (n=80) among LTS patients with confirmed response (76 vs 40 months).

“Updated survival, response, and safety data with 7.5 years minimum follow-up, along with additional subgroup analyses, will be presented,” Tannir said.