Nivolumab monotherapy or in combination with ipilimumab for metastatic melanoma: systematic review and meta-analysis of randomized-controlled trials

Nivolumab, a completely human programmed death-1 inhibitor antibody, was first approved by the Food and Drug Administration for patients with advanced malignant melanoma resistant to other modalities of treatment. In 2015, it received approval as the first line of treatment for malignant melanoma. We aimed to synthesize evidence from published randomized-controlled trials on the safety and efficacy of nivolumab, either alone or in combination with ipilimumab, in the management of advanced unresectable melanoma. We searched the following electronic databases: PubMed, Scopus, Web of Science, and Cochrane Central. The records retrieved were screened for eligibility. Time-to-event data were pooled as Hazard ratio using the generic inverse variance method and dichotomous data were pooled as relative risk (RR) in a random-effects model. We used Review Manager 5.3 software for windows. Four unique randomized-controlled trials (five reports) with a total of 1910 patients (nivolumab group, n=1207 and control group, n=703) were included. The overall effect estimate favored nivolumab plus ipilimumab versus ipilimumab alone in terms of the objective response rate [RR: 3.58, 95% confidence interval (CI): 2.08–6.14], the complete response rate (RR: 5.93, 95% CI: 2.45–14.37), the partial response rate (RR: 2.80, 95% CI: 2.16–3.64), the stable disease rate (RR: 0.56, 95% CI: 0.41–0.76), and progression-free survival (hazard ratio: 0.67, 95% CI: 0.60–0.74). The pooled studies were homogenous. Similar results were obtained for nivolumab monotherapy versus chemotherapy comparison. Nivolumab alone or combined with ipilimumab significantly improved the overall and complete response rates compared with ipilimumab alone. In addition, nivolumab resulted in longer progression-free survival with a comparable safety profile.