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.
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]