Nivolumab plus ipilimumab offers ‘potential for cure’ in advanced melanoma
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Key takeaways:
- The addition of nivolumab to ipilimumab prolonged survival for patients with advanced melanoma.
- Nivolumab monotherapy improved OS vs. ipilimumab monotherapy.
The addition of nivolumab to ipilimumab conferred a long-term OS benefit for patients with advanced melanoma, according to study results presented at ESMO Congress.
Final results of the randomized phase 3 CheckMate --067 trial — based on a decade of follow-up — also showed nivolumab monotherapy significantly improved survival compared with ipilimumab.
“There is now a potential for cure [among] patients responsive to these treatments,” James Larkin, MD, PhD, FRCP, professor and consultant medical oncologist at The Royal Marsden NHS Foundation Trust in London, and colleagues wrote.
Background and methods
The CheckMate -067 trial evaluated the addition of nivolumab (Opdivo, Bristol Myers Squibb) — an anti-PD-1 monoclonal antibody — to the anti-CTLA-4 antibody ipilimumab (Yervoy, Bristol Myers Squibb) for patients with advanced melanoma.
The analysis included 945 patients with previously untreated stage III or stage IV melanoma.
Researchers assigned 314 of them to 1 mg/kg nivolumab plus 3 mg/kg ipilimumab every 3 weeks for four doses, followed by 3 mg/kg nivolumab every 2 weeks. They assigned 316 patients to receive 3 mg/kg nivolumab every 2 weeks plus placebo. The other 315 patients received 3 mg/kg ipilimumab every 3 weeks for four doses.
Treatment continued until disease progression or unacceptable toxicity.
Investigators stratified by PD-L1 status, BRAF mutation status and metastasis stage.
PFS and OS served as co-primary endpoints. Melanoma-specific survival served as a secondary endpoint.
Ten-year results
Previously reported results showed the nivolumab-ipilimumab combination improved objective response, PFS and OS compared with ipilimumab alone.
At ESMO, Larkin and colleagues presented updated findings based on minimum follow-up of 10 years.
Long-term results continued to show a statistically significant improvement in median OS with the combination vs. ipilimumab monotherapy (71.9 months vs. 19.9 months; HR = 0.53; 95% CI, 0.44-0.65).
The survival benefit appeared consistent across subgroups, including those based on PD-L1 expression and BRAF status.
Patients assigned nivolumab monotherapy achieved longer median OS than those assigned ipilimumab (36.9 months vs. 19.9 months; HR = 0.63; 95% CI, 0.52-0.76).
Median melanoma-specific survival had not been reached in the nivolumab-ipilimumab group. Patients assigned nivolumab monotherapy achieved longer median melanoma-specific survival than those assigned ipilimumab (49.4 months vs. 21.9 months).
An analysis of patients who remained progression free for at least 3 years showed superior rates of 10-year melanoma-specific survival with the combination (96%) and nivolumab monotherapy (97%) vs. ipilimumab alone (88%).
Eight patients — four assigned the combination and four assigned nivolumab monotherapy — progressed after more than 5 years of follow-up.
The long-term survival benefit observed among patients who received nivolumab either with ipilimumab or alone highlights how immune checkpoint inhibitors “have transformed the long-term prognosis for patients with advanced melanoma,” Larkin and colleagues wrote.
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Larkin J, et al. Abstract LBA43. Presented at: European Society for Medical Oncology Congress; Sept. 13-17, 2024; Barcelona, Spain.
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