A Comparative Systematic Review of Survival Outcomes for Immune Checkpoint Inhibitors Versus Traditional Chemotherapy in Advanced Melanoma

Abstract

The advent of immune checkpoint inhibitors (ICIs) has transformed the treatment landscape. This systematic review compares the survival outcomes of ICI-based therapies with those of traditional chemotherapy in patients with advanced melanoma. A systematic search of PubMed, Google Scholar, Semantic Scholar, Springer, and Wiley Online Library was conducted to identify randomized controlled trials (RCTs) comparing ICIs (ipilimumab, nivolumab, pembrolizumab) with traditional chemotherapy (e.g., dacarbazine) in patients with unresectable stage III or IV melanoma. Primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary outcomes included objective response rate (ORR), duration of response (DoR), landmark survival rates, safety, and health-related quality of life (HRQoL). The Cochrane Risk of Bias 2 (RoB 2) tool was used for quality assessment. Seventeen RCTs met the inclusion criteria for analysis. Across pivotal trials, ICIs demonstrated a substantial survival advantage over chemotherapy. In treatment-naïve patients, nivolumab reduced the risk of death by 58% compared with dacarbazine (HR = 0.42), and ipilimumab in combination with dacarbazine reduced the risk of death by 28% (HR = 0.72). Long-term follow-up data reveal a plateau in survival curves for ICI-treated patients, with 10-year OS rates approaching 50% for combination immunotherapy—a phenomenon not observed with chemotherapy. ICIs also yielded higher and more durable tumor responses. The safety profiles were distinct: chemotherapy was associated with myelosuppression and nausea, whereas ICIs were characterized by immune-related adverse events (irAEs). The results confirm a paradigm shift in the management of advanced melanoma.