KEY TAKEAWAYS
- The CheckMate 214 phase III trial aimed to assess survival, response rates, and safety in diverse RCC patients, focusing on long-term survival.
- The primary endpoints were OS, PFS, and ORR.
- The results demonstrated that NIVO+IPI showed prolonged survival and more lasting response benefits than SUN across various patient groups.
In CheckMate 214, first-line nivolumab plus ipilimumab(NIVO+IPI) has shown significant long-term survival advantages compared to sunitinib(SUN) in patients with advanced renal cell carcinoma (aRCC).
Nizar M. Tannir and his team spearheaded the study that aimed to present survival, response, and safety data after at least 6 years of follow-up, stratified by International Metastatic RCC Database Consortium (IMDC) risk and among long-term survivors.
Patients with clear cell aRCC were assigned in a 1:1 ratio to receive either NIVO 3 mg/kg + IPI 1 mg/kg every 3 weeks for 4 cycles followed by NIVO 3 mg/kg every 2 weeks or SUN 50 mg once daily for 4 weeks on and 2 weeks off.
Primary endpoints included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) per independent radiology review committee (IRRC) using RECIST v1.1 in intermediate/poor risk (IP) patients per the IMDC criteria. Secondary endpoints were assessed in the intent-to-treat (ITT) population, and exploratory outcomes were evaluated in favorable risk (FAV) patients. Additionally, exploratory outcomes in long-term survivors (LTS) were analyzed post hoc.
In the ITT population, OS with NIVO+IPI remained superior to SUN, with an HR of 0.72. Similar findings were observed in IP patients, with an HR of 0.68. Conversely, OS benefits between treatment arms were comparable in FAV patients, with an HR of 0.87. Median PFS was consistent with previous findings. The ORR per IRRC was higher with NIVO+IPI than SUN, with more ongoing responses observed in ITT (60% vs. 50%) and IP (60% vs. 50%) patients.
In FAV patients, although the ORR was lower with NIVO+IPI versus SUN, more responses were still ongoing (59% vs. 52%, respectively). Furthermore, regardless of the IMDC risk, NIVO+IPI exhibited a longer median duration of response (DOR) and a higher complete response (CR) rate than SUN.
The incidence of any and grade 3-4 treatment-related adverse events (TRAEs) remained mostly consistent. A single additional drug-related death was reported with NIVO+IPI, while none occurred with SUN since the previous database lock. In the LTS subgroup (NIVO+IPI, n = 208; SUN, n = 151), the ORR was higher (66% vs. 53%) with more CR observed (27% vs. 9%) and fewer progressions (4% vs. 11%) in patients treated with NIVO+IPI compared to SUN.
Among LTS with confirmed response, the median DOR was longer with NIVO+IPI (n = 137) compared to SUN (n = 80) (76 vs. 40 months). Updated survival, response, and safety data with a minimum follow-up of 7.5 years, along with additional subgroup analyses, will be presented.
The study concluded that NIVO+IPI showcased prolonged survival and enhanced response durability compared to SUN across ITT and IP patients. Moreover, regardless of the IMDC risk group, NIVO+IPI also exhibited higher CR rates and longer median DOR in LTS. Importantly, no new safety signals emerged. Research was funded by Bristol-Myers Squibb.
Source: https://meetings.asco.org/abstracts-presentations/229890
Clinical Trial: https://clinicaltrials.gov/study/NCT02231749
Tannir NM, Escudier B, McDermott DF, et al. (2024) ‘’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.’’ J Clin Oncol 42, 2024 (suppl 4; abstr 363) DOI: 10.1200/JCO.2024.42.4_suppl.363.
