First-Line Nivolumab/Ipilimumab Yields Impressive Treatment-Free Survival in Advanced Renal Cell Carcinoma

Patients with advanced renal cell carcinoma who received first-line nivolumab and ipilimumab experienced an improved treatment-free survival vs sunitinib.

Treatment with nivolumab (Opdivo) and ipilimumab (Yervoy) resulted in an improved treatment-free survival (TFS) compared with sunitinib (Sutent) in patients with advanced renal cell carcinoma, according to the results of the phase 3 CheckMate-214 trial (NCT02231749).1

Forty-two months following randomization, investigators reported that among intermediate- and poor-risk patients, 52% of those receiving the combination regimen and 39% of those receiving the monotherapy were alive. Additionally, 18% and 4.9% of patients in each group, respectively, were alive. In the favorable-risk population, 70.1% of those treated with nivolumab/ipilimumab and 73% in the sunitinib cohort were alive, 20% and 9% of whom, respectively, were treatment-free. The mean TFS was 6.9 months in the combination arm vs 3.1 months in the monotherapy arm.

“This analysis is very patient-centered, and the implications of this work are that we have a new way to assess the value of new treatments to patients when we do clinical trials. We knew from the previous CheckMate-214 analysis that nivolumab plus ipilimumab improved survival compared with sunitinib; now, we are able to compare the way patients spent that overall survival time on these two different treatment approaches, and I think having this information is an important complement to the original trial results,” Meredith Regan, ScD, an associate professor at Harvard Medical School and Dana-Farber Cancer Institute, said in a press release.2

Investigators enrolled 1096 patients who were treatment-naïve with primarily clear cell histology. Patient were randomized 1:1 to receive either 3 mg/kg per body weight of nivolumab plus 1 mg/kg of ipilimumab every 3 weeks followed by 3 mg/kg of nivolumab every 2 weeks (n = 550) or 50 mg of sunitinib once daily for 4 weeks of every 6-week cycle (n = 546). Treatment continued until disease progression or unacceptable toxicity.

Additional findings from the study indicated that the 42-month mean TFS without toxicity was twice as long in the combination group than the single-agent group. The difference in TFS without grade 3 or higher treatment-related adverse effects (TRAEs) was 3.4 months (95% CI, 2.2-4.6) and 2.4 months for grade 2 or higher TRAEs, respectively. Grade 2 or higher TRAEs that continued or were new following therapy discontinuation yielded a 42-month TFS plus toxicity of 3.0 months in the nivolumab/ipilimumab arm compared with 1.6 months in the sunitinib arm.

The mean 42-month TFS in the favorable-risk population was 11.0 months in the combination arm compared with 3.7 months in the single-agent arm. The shorter 7.3-month difference was attributed to a shorter mean protocol duration for the nivolumab/ipilimumab group (14.0 months) compared with the sunitinib group (20.2 months). Despite the mean TFS with grade 2 or higher TRAEs being long with the combination arm (4.1 months vs 1.4 months), investigators noted that the mean TFS without toxicity was longer in the nivolumab/ipilimumab cohort (6.9 months) than in the sunitinib group (2.3 months).

“As we continue to develop new treatments, we have an opportunity to think about new methods to better balance the efficacy and toxicity to the patients. To do that, we needed a new endpoint to quantify those 2 aspects together—to continue to improve survival for patients while also focusing on how they are spending their time. That’s how TFS came to be,” Regan concluded.


  1. Regan MM, Jegede OA, Mantia CM, et al. Treatment-free survival after immune checkpoint inhibitor therapy versus targeted therapy for advanced renal cell carcinoma: 42-month results of the CheckMate 214 trial. Clin Can Res. Published online November 10, 2021. doi:1158/1078-0432.CCR-21-2283
  2. Immunotherapy may yield longer treatment-free survival than targeted therapy in advanced renal cell carcinoma patients. News release. American Association for Cancer Research. November 10, 2021. Accessed November 24, 2021.