Sex as a predictor of response to cancer immunotherapy.

Abstract

In their meta-analysis of 20 randomised controlled trials in The Lancet Oncology, Fabio Conforti and colleagues 1 Conforti F Pala L Bagnardi V et al. Cancer immunotherapy efficacy and patients' sex: a systematic review and meta-analysis. Lancet Oncol. 2018; 19: 737-746 Summary Full Text Full Text PDF PubMed Scopus (284) Google Scholar found that the magnitude of immune checkpoint inhibitor benefit is largely sex-dependent. This finding might have potential implications for clinical practice, but several points of this study need to be discussed. Cancer immunotherapy efficacy and patients' sex: a systematic review and meta-analysisImmune 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. Full-Text PDF Sex as a predictor of response to cancer immunotherapyFabio Conforti and colleagues1 reported that the efficacy of immunotherapies in solid tumours differs between sexes. The authors systematically reviewed 20 randomised controlled trials, concluding that men would benefit more than women from treatment with checkpoint inhibitors (pooled overall survival hazard ratio [HR] 0·72 vs 0·86, p=0·0019). We believe that this conclusion is misleading, biased, and is of limited value for clinical practice. Full-Text PDF Sex as a predictor of response to cancer immunotherapyFabio Conforti and colleagues did a meta-analysis1 to investigate the effect of sex on overall survival in patients treated with immunotherapy, and found that the hazard ratio for men treated with immunotherapy versus control treatment was lower than that of women. The authors conclude that a difference in efficacy exists between men and women treated with immune checkpoint inhibitors, which favours men, and that future research should focus on improving the effectiveness of immunotherapies in women. Full-Text PDF Sex as a predictor of response to cancer immunotherapyFabio Conforti and colleagues did a meta-analysis1 to assess heterogeneity in efficacy of immune checkpoint inhibitors between men and women. The primary outcome was overall survival. The authors included 20 randomised controlled trials in their meta-analysis, in which the hazard ratio (HR) was used to quantify the treatment effect for each study and sex. A random-effects model was used to obtain a pooled HR for the overall treatment effect for each sex. Therefore, the 20 individual HRs were assumed to be a random sample from a hypothetical, super-population (ie, HRs from all current and future comparative trials of this type of intervention in similar patient populations) with a log-normal distribution. Full-Text PDF Sex as a predictor of response to cancer immunotherapy – Authors' replyTao Zhang and colleagues claim that the conclusions of our meta-analysis1 cannot be extended to populations different from those enrolled in the 20 randomised controlled trials (RCTs) analysed, such as patients treated with immunotherapies other than cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death receptor-1 (PD-1) inhibitors. This point is obvious and is acknowledged in our paper: the main message of our work is that new anticancer immunotherapies must be tested taking into account the potential effect of patients' sex in influencing treatments' efficacy. Full-Text PDF Sex as a predictor of response to cancer immunotherapyWe read with great interest the meta-analysis by Fabio Conforti and colleagues,1 which investigated how patient sex affects response to immune checkpoint inhibitors. The meta-analysis of 20 randomised controlled trials led to authors to conclude that men benefit more than women with regard to overall survival. This finding suggests that mechanisms of anti-tumor immunity induced by immunotherapeutic approaches might differ between men and women. Full-Text PDF Sex as a predictor of response to cancer immunotherapyWe read with interest the systematic review and meta-analysis by Fabio Conforti and colleagues.1 The authors reviewed 20 randomised controlled trials of immune checkpoint inhibitors (ipilimumab, tremelimumab, nivolumab, or pembrolizumab) including more than 11 000 patients, finding a relative reduction in the risk of death resulting from immunotherapy compared with standard therapies, which was significantly higher in male than in female patients. The pooled overall survival hazard ratio (HR) was 0·72 (95% CI 0·65–0·79) for men versus 0·86 (0·79–0·93) for women, with a significant difference in treatment efficacy identified between the two sexes (p=0·0019). Full-Text PDF