In a systematic review and meta-analysis reported in The Lancet Oncology by Fabio Conforti, MD, of the Division of Medical Oncology for Melanoma & Sarcoma, European Institute of Oncology, Milan, and colleagues, a significant difference in overall survival benefit favoring male vs female patients receiving immune checkpoint inhibitor therapy for advanced cancers was reported.
The study involved database searches of the literature through November 2017 for randomized controlled trials of immune checkpoint inhibitors that included hazard ratios (HRs) for death according to patient sex. A total of 20 trials of ipilimumab (Yervoy), tremelimumab, nivolumab (Opdivo), and pembrolizumab (Keytruda) were identified, including a total of 11,351 patients with advanced or metastatic disease. Of them, 7,646 (67%) were men and 3,705 (33%) were women; the most common types of cancer were melanoma (n = 3,632, 32%) and non–small cell lung cancer (n = 3,482, 31%).
Among all patients, 2,881 were enrolled in ipilimumab trials; 1,226, in tremelimumab trials; 3,893, in nivolumab trials; 3,209, in pembrolizumab trials; and 142, in a nivolumab plus ipilimumab trial.
Survival by Sex
Among all patients, the pooled overall survival hazard ratios were 0.72 (95% confidence interval [CI] = 0.65–0.79) for immune checkpoint inhibitor vs control treatment in male patients and 0.86 (95% CI = 0.79–0.93) in female patients. The difference in efficacy between men and women receiving immune checkpoint inhibitors was significant (P = .0019), with the pooled interaction hazard ratio for men vs women being 0.85. Subgroup analyses for cancer type (P = .72 for heterogeneity); line of treatment (P = .77 for heterogeneity); type of immune checkpoint inhibitor (anti–programmed cell death protein 1 [PD-1], anti–cytotoxic T-lymphocyte–associated protein 4 (CTLA-4); P = .40 for heterogeneity); and control group (immunotherapy, no immunotherapy; P = .72) showed better hazard ratios for men vs women for each subgroup, with the heterogeneity test for the sex interaction being nonsignificant in each subgroup.
The investigators concluded, “Immune checkpoint inhibitors can improve overall survival for patients with advanced cancers such as melanoma and non–small cell lung cancer, but the magnitude of benefit is sex-dependent. Future research should guarantee greater inclusion of women in trials and focus on improving the effectiveness of immunotherapies in women, perhaps exploring different immunotherapeutic approaches in men and women.” ■