Nivolumab-ipilimumab combination confers durable benefit in advanced renal cell carcinoma
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First-line nivolumab plus ipilimumab conferred durable survival benefit compared with sunitinib for patients with advanced renal cell carcinoma, according to results of the randomized phase 3 CheckMate- 214 trial.
The findings — presented at the virtual ESMO Congress 2021 — showed nearly half of patients assigned the combination remained alive at 5 years.
“Historically, the 5-year survival rate for those diagnosed with advanced or metastatic renal cell carcinoma has been poor,” Robert J. Motzer, MD, kidney cancer section head and Jack and Dorothy Byrne chair in clinical oncology at Memorial Sloan Kettering Cancer Center, told Healio. “Initial results from CheckMate- 214 evaluating [nivolumab (Opdivo, Bristol Myers Squibb)] plus [ipilimumab (Yervoy, Bristol Myers Squibb)] in advanced renal cell carcinoma that were shared in 2017 marked a significant change in the standard of care. This year at ESMO, we have follow-up results that represent the longest median overall survival currently reported in a phase 3 trial of patients with previously untreated advanced or metastatic renal cell carcinoma.”
Nivolumab is an anti-PD-1 antibody and ipilimumab is an anti-CTLA-4 antibody.
CheckMate- 214 included 1,096 treatment-naive patients with advanced renal cell carcinoma.
Researchers randomly assigned 550 patients to 3 mg/kg nivolumab plus 1 mg/kg ipilimumab every 3 weeks for four doses, followed by 3 mg/kg nivolumab every 2 weeks. The other 546 patients received 50 mg daily sunitinib (Sutent, Pfizer) — a multitargeted tyrosine kinase inhibitor — in a 4-weeks-on, 2-weeks-off schedule.
OS, PFS and objective response rate among patients with intermediate- or poor-risk disease, the intent-to-treat population and those with favorable-risk disease served as key trial endpoints.
The FDA approved the nivolumab-ipilimumab combination for intermediate- or poor-risk patients with previously untreated advanced renal cell carcinoma based on results after minimum follow-up of 17.5 months, which showed improved OS (median, not reached vs. 26 months; HR = 0.63; P < .001), ORR (42% vs. 27%; P < .001) and PFS (median, 11.6 months vs. 8.4 months) over sunitinib.
At ESMO, Motzer presented updated data based on median follow-up of 67.7 months.
Analyses of patients with intermediate- or poor-risk disease showed continued benefit with nivolumab-ipilimumab vs. sunitinib with regard to OS (median, 47 months vs. 26.6 months; HR = 0.68; 95% CI, 0.58-0.81). Five-year OS rates were 43% with the combination and 31% with sunitinib.
The combination also continued to appear superior with regard to ORR (42% vs. 27%), complete response rate (11% vs. 2%) and duration of response (median, not reached vs. 19.7 months).
Analyses of the intention-to-treat population also favored nivolumab-ipilimumab with regard to median OS (55.7 months vs. 38.4 months; HR = 0.72; 95% CI, 0.62-0.85), 5-year OS (48% vs. 37%), ORR (39% vs. 32%), complete response rate (12% vs. 3%) and duration of response (median, not reached vs. 24.8 months).
“[Although] the median duration of response has not yet been reached with nivolumab plus ipilimumab, the data show some durable effects of this combination for patients living with this disease,” Motzer said in a Bristol Myers Squibb-issued press release.
Motzer also presented outcomes of conditional survival analyses, which estimated the probability that patients would achieve certain outcomes after reaching specific milestones in their treatment.
Among patients who remained alive 3 years after starting treatment, probability of remaining alive for an additional 2 years was higher in the nivolumab-ipilimumab group (81% vs. 72%).
Among patients who remained progression-free for 3 years after starting treatment, probability of remaining progression-free for an additional 2 years was higher in the nivolumab-ipilimumab group (89% vs. 57%).
Among patients who responded to treatment and remained in response for 3 years, probability of remaining in response for an additional 2 years was higher with the nivolumab-ipilimumab combination (89% vs. 63%).
The nivolumab-ipilimumab combination exhibited a manageable safety profile, and researchers observed no new safety signals during extended follow-up.
“These data reinforce the proven benefits of dual PD-1 and CTLA-4 inhibition, with Opdivo plus Yervoy maintaining superior overall survival and response benefits vs. sunitinib in both patients with intermediate- and poor-risk prognostic factors, the primary endpoint population, and across all randomized patients,” Motzer told Healio. “These 5-year results also add to the evidence we have seen for Opdivo-plus-Yervoy-based combinations to significantly improve survival expectations across several other tumor types, including mesothelioma, non-small cell lung cancer, metastatic melanoma and esophageal squamous cell carcinoma.”
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Motzer RJ, et al. Abstract 661P. Presented at: European Society for Medical Oncology Congress (virtual meeting); Sept. 17-21, 2021.
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