Immunotherapy combination confers durable benefit in advanced renal cell carcinoma
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First-line nivolumab plus ipilimumab conferred greater long-term clinical benefit than sunitinib for patients with advanced renal cell carcinoma, according to study results presented at International Kidney Cancer Symposium.
Benefit with the combination persisted among patients with intermediate/poor-risk or favorable-risk disease per International Metastatic RCC Database Consortium (IMDC) criteria, Nizar M. Tannir, MD, FACP, professor in the department of genitourinary medical oncology at The University of Texas MD Anderson Cancer Center, and colleagues found.
Nivolumab (Opdivo, Bristol Myers Squibb) is an anti-PD-1 antibody and ipilimumab (Yervoy, Bristol Myers Squibb) is an anti-CTLA-4 antibody.
The randomized phase 3 CheckMate 214 trial compared the combination with sunitinib (Sutent, Pfizer), a multitargeted tyrosine kinase inhibitor.
CheckMate 214 included 1,096 treatment-naive patients with advanced clear-cell 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 in a 4-weeks-on, 2-weeks-off schedule.
OS, PFS and objective response rate in the intent-to-treat population, those with intermediate-poor risk disease and those with favorable-risk disease served as key trial endpoints.
The FDA approved the nivolumab-ipilimumab combination for patients with previously untreated intermediate/poor-risk advanced renal cell carcinoma based on results after minimum follow-up of 17.5 months. At that time, results 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) with the combination.
Updated results presented at this year’s virtual ESMO Congress — based on median follow-up of 67.7 months of follow-up — showed patients with intermediate/poor-risk disease continued to derive a long-term OS benefit with nivolumab-ipilimumab vs. sunitinib (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 appeared 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).
Outcomes in the intent-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).
Tannir and colleagues conducted post hoc exploratory analyses of long-term survivors — defined as those who survived at least 5 years — to assess outcomes by intermediate/poor vs. favorable IMDC risk. These analyses included 236 patients assigned nivolumab-ipilimumab (intermediate/poor risk, n = 163; favorable risk, n = 73) and 171 patients assigned sunitinib (intermediate/poor risk, n = 112; favorable risk, n = 59).
Among patients assigned nivolumab-ipilimumab, long-term survivors appeared more likely to have smaller target lesions and less likely to have bone metastases than the intention-to-treat population. Otherwise, baseline characteristics appeared similar between groups.
Among all long-term survivors, researchers reported a higher confirmed ORR with nivolumab-ipilimumab than sunitinib (61% vs. 56%).
Results showed higher rates of complete response (intermediate/poor risk, 25% vs. 6%; favorable risk, 22% vs. 14%) and shorter median time to response (intermediate/poor risk, 2.8 months vs. 4 months; favorable risk, 2.8 months vs. 4.2 months). Durations of confirmed response favored the nivolumab-ipilimumab regimen among all long-term survivors, those with intermediate/poor-risk disease and those with favorable-risk disease.
Analysis of long-term survivors who achieved complete response showed a higher percentage of patients assigned nivolumab-ipilimumab than sunitinib achieved treatment-free interval (intermediate/poor risk, 54% vs. 14%; favorable risk, 43% vs. 10%). Median treatment-free interval in the intermediate/poor-risk group were 42 months (range, 4-68) with nivolumab-ipilimumab vs. 43 months (range, 16-60) with sunitinib. Median treatment-free interval in the favorable-risk group was 59 months (range, 7-68) with nivolumab-ipilimumab vs. 47 months (range, 4-62) with sunitinib.
A lower percentage of long-term survivors assigned nivolumab-ipilimumab than sunitinib required subsequent systemic therapy (intermediate/poor risk, 39% vs. 75%; favorable risk, 68% vs. 83%).
In the overall study population, 23% of patients assigned nivolumab-ipilimumab and 13% of those assigned sunitinib experienced treatment-related adverse events that led to discontinuation.
In the long-term survivors group, 28% of patients treated with nivolumab-ipilimumab and 16% of those treated with sunitinib experienced treatment-related adverse events that led to discontinuation. This showed that discontinuation due to treatment-related adverse events did not preclude patients from surviving at least 5 years, Tannir said.
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Tannir N, et al. Abstract CTR11. Presented at: International Kidney Cancer Symposium; Nov. 5-6, 2021; Austin, Texas.
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