The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China
Fang Yang , Yucai Wang , Grzegorz S. Nowakowski , Michael Wang , Ashish V. Chintakuntlawar , Thorvardur Ragnar Halfdanarson , Lance C. Pagliaro , Jia Wei , Baorui Liu , Julian R. Molina , Svetomir Markovic
Background: Sex, age and ECOG performance status (PS) may affect immune response and the efficacy of cancer immunotherapy with immune checkpoint inhibitors (ICI). We did a meta-analysis to assess the potential sex, age and ECOG PS differences of immunotherapy efficacy in advanced cancer. Methods: PubMed was searched up to January 15, 2019 for randomized controlled trials (RCT) comparing overall survival (OS) in patients with advanced cancer treated with ICI immunotherapy vs control therapy (without ICI). For sex difference analysis, pooled hazard ratio (HR) of death for men and women was calculated separately, and the heterogeneity between the two estimates was assessed using an interaction test by pooling study-specific interaction HR. Age ( < 65 vs ≥65) and ECOG PS (0 vs ≥1) difference was analyzed similarly. Subgroup analysis by cancer type and line of therapy (frontline vs subsequent) was explored. All analyses were done in Comprehensive Meta Analysis (v2) with random effects models. Results: Thirty phase 2/3 RCTs involving 17,728 patients were included. An OS benefit of immunotherapy was found for both men (HR 0.75, 95% confidence interval [CI] 0.69-0.81, P< 0.01) and women (HR 0.79, 95% CI 0.69-0.90, P< 0.01); for both younger ( < 65; HR 0.75, 95% CI 0.68-0.83, P< 0.01) and older (≥65; HR 0.76, 95% CI 0.69-0.83, P< 0.01) patients; and for both ECOG PS 0 (HR 0.78, 95% CI 0.69-0.89, P< 0.01) and PS ≥1 (HR 0.77, 95% CI 0.71-0.84, P< 0.01) patients. No significant difference of relative benefit from immunotherapy over control therapy was found in patients with different sex (P = 0.283), age (P = 0.906) or ECOG PS (P = 0.783). In melanoma RCTs, compared with women (HR 0.77, 95% CI 0.64-0.94, P< 0.01), men (HR 0.56, 95% CI 0.42-0.76, P< 0.01) had more OS benefit from immunotherapy (P = 0.037). No significant difference was found in other subgroup analyses by cancer types or line of therapy. Conclusions: Overall we found no evidence of association of sex, age, or ECOG PS with cancer immunotherapy efficacy. However, in melanoma, men might benefit more from immunotherapy than women.
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