Impact of clinicopathological characteristics on survival in patients treated with immune checkpoint inhibitors for metastatic melanoma

Immune checkpoint inhibitors (ICIs) have unprecedented effects on the treatment of metastatic melanoma. However, little is known about the prognostic values of various clinicopathological characteristics. Here, PubMed, Embase and Cochrane database were searched from inception to April 2018 for random controlled trials (RCTs) that compared ICIs with controls. The hazard ratios (HRs) for overall survival (OS) according to gender, age, Eastern Cooperative Oncology Group (ECOG) performance status (PS), lactate dehydrogenase (LDH) level and metastasis stage were extracted. Four phase III RCTs involving 1,598 patients with metastatic melanoma were included in this study. Compared with conventional agents, ICIs were associated with prolonged OS (HR, 0.67; 95% CI, 0.50-0.88; p = 0.005). The pooled OS HR was 0.60 (95% CI, 0.42-0.84; p = 0.003) in men; 0.84 (95% CI, 0.69-1.01; p = 0.07) in women. The difference in efficacy between men and women was significant (p(interaction) = 0.03). The OS HR was 0.59 (95% CI, 0.41-0.83; p = 0.003) in patients >65 years old; 0.74 (95% CI, 0.55-1.01; p = 0.054) in patients <65 years old. The OS HR was 0.75 (95% CI, 0.60-0.94; p = 0.01) in patients with ECOG PS = 1; 0.64 (95% CI, 0.38-1.06; p = 0.08) in patients with ECOG PS = 0. Additionally, the long-term benefits were independent of metastasis stage and LDH level. In summary, although immunotherapy significantly prolongs OS in metastatic melanoma, the long-term benefits in women, younger patients (<65 years old) and patients with ECOG PS = 0 were marginal. These results may assist in treatment decision-making, design and interpretation of clinical trials and economic analyses.