News

Article

Nivolumab/ipilimumab continues to show improved survival, durable response in aRCC

Author(s):

Fact checked by:

Key Takeaways

  • Nivolumab plus ipilimumab improved overall survival and response rates over sunitinib in advanced renal cell carcinoma, with a median follow-up of 9.3 years.
  • The combination showed sustained benefits in overall survival, progression-free survival, and duration of response, especially in intermediate and poor-risk patients.
SHOW MORE

"This final analysis of this study continues to support nivo+ipi as a standard of care for patients with untreated RCC," says Robert J. Motzer, MD.

First-line nivolumab (Opdivo) plus ipilimumab (Yervoy) continued to show improved survival and durable response benefits vs sunitinib (Sutent) in patients with previously untreated advanced renal cell carcinoma (aRCC), according to final results from the phase 3 CheckMate-214 trial (NCT02231749) presented at the 2025 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois.1

In total, the CheckMate-214 trial enrolled 1096 patients with aRCC who were randomly assigned 1:1 to receive nivolumab plus ipilimumab or sunitinib. Initial data from the trial, which led to FDA approval of the combination in April 2018, showed that nivolumab plus ipilimumab significantly improved overall survival (OS) and objective response rate (ORR) vs sunitinib in this population.

Robert J. Motzer, MD

Robert J. Motzer, MD

Robert J. Motzer, MD, of Memorial Sloan Kettering Cancer Center, presented data on the final analysis of the trial, which is the longest follow-up (median follow-up, 9.3 years) of a first-line checkpoint inhibitor combination in aRCC.

In patients with IMDC intermediate or poor-risk, data showed sustained benefits OS, progression-free survival, and duration of response (DOR) with the nivo/ipi combination.

In these patients, the median OS was 46.7 months (95% CI, 35.0 to 55.7) in the nivo/ipi arm vs 26.0 months (95% CI, 21.8 to 32.6) in the sunitinib arm (HR, 0.69; 95% CI, 0.59 to 0.81). Median PFS was 12.4 months (95% CI, 8.7 to 16.8) in the treatment arm vs 8.5 months (95% CI, 7.0 to 11.1) in the sunitinib arm (HR, 0.73; 95% CI, 0.61 to 0.87). Additionally, the median DOR was 82.8 months (95% CI, 54.1 to NE) in the nivo/ipi arm vs 19.8 months (95% CI, 16.4 to 26.4) in the sunitinib arm (HR, 0.48; 95% CI, 0.33 to 0.69).

In the IMDC favorable-risk population, nivo/ipi was associated with a 13% improvement in OS at 9 years (HR, 0.80).

Motzer added, “Sunitinib still is the winner in progression-free survival compared to nivo/ipi. When responses do occur with nivo/ipi, they're considerably more durable.”

There was also an OS advantage with nivo/ipi observed in the intent to treat (ITT) population. At a median follow-up of 9 years, the median OS was 52.7 months (95% CI, 45.8 to 64.4) in the nivo/ipi arm vs 37.8 months (95% CI, 31.9 to 43.8) in the sunitinib arm (HR, 0.71; 95% CI, 0.62 to 0.82). The OS benefit was consistent across subgroups within the ITT population, including in the intermediate-risk group and those with sarcomatoid features.

The advantage in PFS with nivo/ipi in the ITT population was also maintained from 24 months onward. At a median of 9 years of follow-up, the median PFS was 12.4 months (95% CI, 9.9 to 16.6) in the nivo/ipi arm vs 12.3 months (95% CI, 9.8 to 15.2) in the sunitinib arm (HR, 0.88; 95% CI, 0.76 to 1.04).

The combination of nivo/ipi also demonstrated improvements in ORR vs sunitinib in both the ITT population and in patients with IMDC intermediate/poor risk. In the ITT population, the ORR was 39.5% with nivo/ipi vs 33.0% with sunitinib. Likewise, in the intermediate/poor risk population, the ORR was 42.4% in the nivo/ipi arm vs 27.5% in the sunitinib arm.

At the time of data report, 58% of patients in the ITT population and 59% of patients in the IMDC intermediate/poor risk population who received nivo/ipi remain in response. Further, 80% of patients in the ITT population and 84% of patients in the IMDC intermediate/poor risk population had an ongoing complete response.

Data also showed a DOR benefit with nivo/ipi vs sunitinib. Specifically, the median DOR was 76.2 months (95% CI, 59.0 to NE) in the nivo/ipi arm vs 25.1 months (95% CI, 19.8 to 33.2) in the sunitinib arm (HR, 0.53; 95% CI, 0.38 to 0.73).

Nearly all patients on trial had discontinued study therapy at the time of this analysis. Discontinuation due to disease progression was reported in 49% of patients in the nivo/ipi arm and 68% of patients in the sunitinib arm.

Treatment-related adverse events (AEs) were observed in 94% of patients in the nivo/ipi arm and 98% of patients in the sunitinib arm. Grade 3 or higher events were reported in 49% of patients in the nivo/ipi arm and 64% of patients in the sunitinib arm.

Immune-mediated AEs (imAEs) were as expected, according to Motzer, with the most common being related to GI, skin, thyroid, and liver. Most imAEs occurred early in the course of treatment. Overall, 31% of patients in the nivo/ipi arm received corticosteroids to manage imAEs.

“In summary, CheckMate-214 provides the longest reported follow-up to date of any immune-oncology combination therapy for first-line clear cell RCC,” Motzer concluded during the presentation. “This final analysis of this study continues to support nivo+ipi as a standard of care for patients with untreated RCC. In addition, subcutaneous nivolumab has been reported to show clinical equipoise to standard IV dosing and can be considered as an alternative for maintenance nivolumab, following nivo+ipi doublet in patients with advanced RCC.”

 

REFERENCE

1. Choueiri T, Escudier B, McDermott D, et al. Nivolumab plus ipilimumab vs sunitinib for first-line treatment of advanced renal cell carcinoma: Final analysis from the phase 3 CheckMate 214 trial. J Clin Oncol. 2025;43 (suppl 17; abstr 4505). doi:10.1200/JCO.2025.43.16_suppl.4505

Newsletter

Stay current with the latest urology news and practice-changing insights — sign up now for the essential updates every urologist needs.

© 2025 MJH Life Sciences

All rights reserved.