KEY TAKEAWAYS
- CheckMate 914 is a phase 3, double-blind, randomized trial that assessed the efficacy and safety of adjuvant nivolumab plus ipilimumab versus placebo for patients with clear localized cell RCC patients and high risk of relapse after radical or partial nephrectomy.
- The trial enrolled 816 patients from 145 hospitals and cancer centers across 20 countries. Patients were randomly assigned (1:1) to receive nivolumab plus ipilimumab or a placebo.
- With a median follow-up of 37 months, the trial found that adjuvant therapy with nivolumab plus ipilimumab did not improve disease-free survival versus placebo in patients with localized renal cell carcinoma at high risk of recurrence after nephrectomy.
- The trial found that nivolumab plus ipilimumab was associated with a higher incidence of grade 3–5 adverse events than placebo. All-cause adverse events of any grade led to the discontinuation of nivolumab plus ipilimumab in 32% of treated patients.
- These results suggest that adjuvant therapy with nivolumab plus ipilimumab may not be an effective treatment option for patients with resected localized renal cell carcinoma.
Patients undergoing resection of localized renal cell carcinoma (RCC) are currently only offered surveillance as standard care, despite an unmet need for effective adjuvant therapy. Here they provide the results of the first arm of a randomized, placebo-controlled trial comparing the effectiveness and safety of adjuvant nivolumab + ipilimumab to the standard of care.
Clear cell renal cell carcinoma patients at high risk of relapse following radical or partial nephrectomy were enrolled in the phase 3 CheckMate 914 study between 4 and 12 weeks prior to random assignment. The work described in Part A was carried out at 145 cancer centers and hospitals in 20 countries. Participants were assigned to receive either nivolumab (240 mg intravenously every 2 weeks for 12 doses) with ipilimumab
(1 mg/kg intravenously every 6 weeks for four doses) or a matching placebo via an interactive response technology system.
Treatment was planned to last for 24 weeks but might be extended up to week 36 if necessary. TNM stage and nephrectomy were used to determine how participants were randomly assigned (partial vs radical). According to the blinded central review, disease-free survival was the primary endpoint, with safety as the secondary endpoint. All patients assigned to receive study medication were analyzed for progression-free survival; patients who got any dose were analyzed for exposure, safety, and tolerability (all-treated population).
Adjuvant nivolumab with ipilimumab (405 patients) or placebo (316 patients) was randomly assigned to 816 patients between August 28, 2017, and March 16, 2021 (411 patients). Around 580 (71%) of the 816 patients were men, while 236 (29%) were women. Median disease-free survival was not reached in the nivolumab plus ipilimumab group, while it was 50 months (95% confidence interval [CI] 48 months to not estimable) in the placebo group (hazard ratio [HR] 0.92, 95% CI [CI] 0.71-0.19; p=0.53).
At the time of the data cutoff, there had been just 61 occurrences, far fewer than what was needed for the interim overall survival analysis (33 in the nivolumab plus ipilimumab group and 28 in the placebo group). Grade 3-5 adverse events occurred in 155 (38%) of 404 individuals who received nivolumab plus ipilimumab and in 42 (10%) of 407 patients who received placebo. In the total number of patients treated, 129 (32%) of those given nivolumab + ipilimumab, and 9 (2%) of those given placebo, discontinued treatment due to adverse events of any grade. The combination of nivolumab and ipilimumab was linked to four deaths, while the placebo group suffered no fatalities.
Patients with localized renal cell carcinoma at high risk of recurrence following nephrectomy did not benefit from adjuvant therapy with nivolumab + ipilimumab compared to placebo. No evidence from their study suggests that this regimen is effective as adjuvant therapy for renal cell carcinoma.
Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02574-0/fulltext
Clinical trial: https://clinicaltrials.gov/ct2/show/NCT03138512
Motzer, R.J., Russo, P., Grünwald, V., Tomita, Y., Zurawski, B., Parikh, O., Buti, S., Barthélémy, P., Goh, J.C., Ye, D., Lingua, A., Lattouf, J.-B., Albigès, L., George, S., Shuch, B., Sosman, J., Staehler, M., Vázquez Estévez, S., Simsek, B. and Spiridigliozzi, J. (2023). Adjuvant nivolumab plus ipilimumab versus placebo for localized renal cell carcinoma after nephrectomy (CheckMate 914): a double-blind, randomized, phase 3 trial. The Lancet. doi:https://doi.org/10.1016/s0140-6736(22)02574-0.
