First-line treatment for advanced renal cell carcinoma has changed substantially with the use of immune checkpoint inhibitor-based regimens. Long-term follow-up is important to show whether these early survival and response gains are maintained over time.
The final CheckMate 214 analysis reports outcomes with a median follow-up of 9.3 years for nivolumab plus ipilimumab versus sunitinib in previously untreated advanced renal cell carcinoma.
The article, titled “Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: final analysis of efficacy and safety from the phase III CheckMate 214 trial,” was published in Annals of Oncology, Volume 37, Issue 7, in July 2026.
Authors: T.K. Choueiri, L. Albigès, D.F. McDermott, H.J. Hammers, B. Escudier, M. Burotto, E.R. Plimack, C. Porta, S. George, T. Powles, F. Donskov, M.B. Atkins, H. Gurney, C.K. Kollmannsberger, M.-O. Grimm, C. Barrios, D. Castellano, V. Grünwald, Y. Tomita, B.I. Rini, R. Jiang, M. van Kooten Losio, C.-W. Lee, N.M. Tannir, and R.J. Motzer.
CheckMate 214 Trial Design
CheckMate 214 was a global, open-label, randomized phase 3 trial conducted across 175 sites in 28 countries. The study enrolled 1,096 patients with previously untreated advanced or metastatic renal cell carcinoma with a clear-cell component. Patients were randomized 1:1 to receive either:
Nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses, followed by nivolumab maintenance, or sunitinib 50 mg once daily on a 4-weeks-on, 2-weeks-off schedule.
In the intention-to-treat population, 550 patients were assigned to nivolumab plus ipilimumab and 546 to sunitinib. Among patients with IMDC intermediate- or poor-risk disease, 425 were assigned to nivolumab plus ipilimumab and 422 to sunitinib. Among patients with IMDC favorable-risk disease, 125 were assigned to nivolumab plus ipilimumab and 124 to sunitinib.
The primary endpoints were overall survival, progression-free survival, and objective response rate in patients with IMDC intermediate- or poor-risk disease. Progression-free survival and objective response were assessed by an independent radiology review committee using RECIST v1.1.
Read more about Nivolumab (Opdivo) on OncoDaily.
Overall Survival in the Intention-to-Treat Population
In the overall intention-to-treat population, nivolumab plus ipilimumab continued to show an overall survival advantage over sunitinib. Median overall survival was 52.7 months with nivolumab plus ipilimumab compared with 37.8 months with sunitinib. The hazard ratio for death was 0.71, with a 95% confidence interval of 0.62 to 0.82.
At 108 months, overall survival probabilities were 31.4% with nivolumab plus ipilimumab and 19.5% with sunitinib.
Progression-free survival by independent radiology review was similar by median value, at 12.4 months with nivolumab plus ipilimumab and 12.3 months with sunitinib. However, long-term progression-free survival favored the immunotherapy combination, with 96-month progression-free survival probabilities of 22.7% versus 9.0%.
Objective response rate was 39.5% with nivolumab plus ipilimumab and 33.0% with sunitinib. Complete responses were more frequent with nivolumab plus ipilimumab, occurring in 12.0% versus 3.5% of patients.
Responses were also more durable with nivolumab plus ipilimumab. Median duration of response was 76.2 months compared with 25.1 months with sunitinib. At 96 months, the probability of remaining in response was 48.0% versus 19.0%.
Read more about CheckMate 214 Trial Final 9-Year Results at ASCO 2025 on OncoDaily.
Outcomes in IMDC Intermediate- and Poor-Risk Disease
The survival benefit was most clearly maintained in patients with IMDC intermediate- or poor-risk disease. Median overall survival was 46.7 months with nivolumab plus ipilimumab and 26.0 months with sunitinib. The hazard ratio for death was 0.69, with a 95% confidence interval of 0.59 to 0.81.
At 108 months, overall survival probabilities were 30.2% with nivolumab plus ipilimumab and 18.7% with sunitinib.
Median progression-free survival by independent radiology review was 12.4 months with nivolumab plus ipilimumab and 8.5 months with sunitinib. The hazard ratio was 0.73, with a 95% confidence interval of 0.61 to 0.87. At 96 months, progression-free survival probabilities were 25.4% and 8.5%, respectively.
Objective response rate was 42.4% with nivolumab plus ipilimumab and 27.5% with sunitinib. Complete responses occurred in 11.8% versus 2.6% of patients. Median duration of response was 82.8 months with nivolumab plus ipilimumab and 19.8 months with sunitinib. At 96 months, the probability of remaining in response was 50.0% with nivolumab plus ipilimumab compared with 23.0% with sunitinib.
A post hoc RCC-specific survival analysis in the intermediate- and poor-risk population showed median RCC-specific survival of 64.5 months with nivolumab plus ipilimumab and 32.6 months with sunitinib.
Favorable-Risk Disease
In patients with IMDC favorable-risk disease, overall survival patterns shifted later in favor of nivolumab plus ipilimumab. Median overall survival was 77.9 months with nivolumab plus ipilimumab and 66.7 months with sunitinib. The hazard ratio was 0.80, with a 95% confidence interval of 0.59 to 1.09. At 108 months, overall survival probabilities were 35.3% versus 21.8%.
The Kaplan–Meier curves for overall survival crossed after approximately 4 years, favoring nivolumab plus ipilimumab later in follow-up.
Progression-free survival probabilities at 96 months were similar between arms, at 12.5% with nivolumab plus ipilimumab and 11.3% with sunitinib. Objective response rate was lower with nivolumab plus ipilimumab than with sunitinib in this subgroup, at 29.6% versus 51.6%. However, complete responses were more frequent with nivolumab plus ipilimumab, occurring in 12.8% versus 6.5% of patients.
Median duration of response was 61.5 months with nivolumab plus ipilimumab and 33.2 months with sunitinib.
Immune-Mediated Adverse Events and Treatment Discontinuation
Exploratory post hoc analyses evaluated outcomes among patients who discontinued nivolumab plus ipilimumab because of immune-mediated adverse events.
Among patients treated with nivolumab plus ipilimumab, the 108-month overall survival probability was 40.1% in those who discontinued due to immune-mediated adverse events and 29.4% in those who did not. These analyses were descriptive and should be interpreted cautiously because of potential immortal time bias.
Safety
Long-term safety remained consistent with previous CheckMate 214 analyses. Treatment-related adverse events of any grade occurred in 94.1% of patients treated with nivolumab plus ipilimumab and 97.6% of those treated with sunitinib. Grade 3–4 treatment-related adverse events occurred in 48.6% versus 64.1% of patients, respectively.
Treatment-related adverse events leading to discontinuation occurred in 23.8% of patients in the nivolumab plus ipilimumab arm and 13.3% in the sunitinib arm. Deaths due to study drug toxicity occurred in 1.5% of patients treated with nivolumab plus ipilimumab and 0.9% of patients treated with sunitinib.
The most frequent organ systems affected by immune-mediated adverse events with nivolumab plus ipilimumab were gastrointestinal, skin, and endocrine systems. Grade 3–4 immune-mediated adverse events in these systems remained relatively low. Most immune-mediated adverse events occurred during the first 12 months of treatment, with decreasing incidence over time. No new safety signals were identified during long-term follow-up.
Conclusion
With a median follow-up of 9.3 years, the final CheckMate 214 analysis shows durable long-term benefit with nivolumab plus ipilimumab compared with sunitinib in previously untreated advanced renal cell carcinoma.
The benefit was most clearly observed in patients with IMDC intermediate- or poor-risk disease, where nivolumab plus ipilimumab maintained advantages in overall survival, progression-free survival, objective response rate, complete response rate, and duration of response. In favorable-risk disease, results were exploratory and showed later overall survival patterns favoring nivolumab plus ipilimumab, despite a lower objective response rate compared with sunitinib.
These final results support nivolumab plus ipilimumab as an established first-line option in advanced RCC and add long-term evidence for the durability of dual checkpoint inhibition in this setting.
The full article is available in Annals of Oncology.
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