Editor’s note: This article’s title was changed to emphasize that nivolumab does not improve survival among patients who previously received ipilimumab.
Nivolumab, a monoclonal antibody targeting PD-1, does not improve overall survival (OS) among patients with advanced melanoma whose disease progresses after receiving ipilimumab, according to a study published in the Journal of Clinical Oncology.1
Therapy with ipilimumab and BRAF-inhibitors has demonstrated efficacy but more than 50% of patients do not benefit from the combination. The CheckMate 037 trial (ClinicalTrials.gov Identifier: NCT01721746) assessed the efficacy of nivolumab vs chemotherapy in the treatment of advanced melanoma.
Two hundred seventy-two patients were randomly assigned 2:1 to receive nivolumab 3 mg/kg every 2 weeks vs investigator’s choice chemotherapy (ICC; dacarbazine 1000mg/m2 every 3 weeks or carboplatin area under the curve 6 plus paclitaxel 175 mg/m2 every 3 weeks).
Patients were stratified by PD-L1 expression, best prior CTLA-4-therapy response, and BRAF status. The co-primary endpoints of the study were OS and proportion of patients who achieved an objective response rate (ORR).
No significant increases in OS were observed: 16 months (95% CI, 12.9-19.9) for the nivolumab group vs 14 months (95% CI, 11.7-18.2) for the ICC group (hazard ratio [HR], 0.95; 95.54% CI, 0.73-1.24). Median progression-free survival was 3.1 months for nivolumab and 3.7 months for ICC (HR, 1.0; 95.1% CI, 0.78-1.436).
The ORR (27% vs 10%) and median duration of response (32 months vs 13 months) were significantly higher in patients receiving nivolumab vs ICC.
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Adverse events (AEs) occurred similarly as reported in previous studies. The most frequently observed treatment-related AEs for the nivolumab group were skin (38%), gastrointestinal (18), and hepatic (11%) effects.
The authors concluded that “[despite] the lack of survival advantage, nivolumab remains an effective option for PD-1 inhibitor-naive patients who experienced failure with ipilimumab and a BRAF inhibitor if BRAF-mutated.”
- Larkin J, Minor D, D’Angelo S, et al. Overall survival in patients with advanced melanoma who received nivolumab versus investigator’s choice chemotherapy in checkmate 037: a randomized controlled, open-label phase III trial. J Clin Oncol. 2017 Jul 3. doi: 10.1200/JOC.2016.71.8023 [Epub ahead of print]