Sex-based heterogeneity in response to lung cancer immunotherapy: a systematic review and meta-analysis
A partir d'une revue systématique de la littérature (8 essais randomisés), cette méta-analyse évalue, en fonction du sexe, les disparités dans la réponse à une immunothérapie à base d'anti-PD1 ou d'anti-PD-L1 dispensée en complément d'une chimiothérapie, chez des patients atteints d'un cancer du poumon
Background : We previously showed that therapy with anti-CTLA-4 or anti-PD-1 agents was more effective for men as compared with women. However, since the sex-dimorphism of the immune system is complex, involving multiple elements of immune-responses, it is possible that women could derive larger benefit than men from strategies other than therapy with immune checkpoint inhibitors (ICIs) alone. Here we investigated whether women could derive larger benefit than men from the combination of chemotherapy and anti-PD-1 or anti-PD-L1.
Methods : We performed two meta-analyses. First, including all RCTs testing anti-PD1/ anti-PD-L1 plus chemotherapy versus chemotherapy, to assess different efficacy between men and women. Second, including all RCTs of first-line systemic treatment in advanced NSCLC testing anti-PD-1/PD-L1 given either alone or combined with chemotherapy to assess different efficacy of these two immunotherapeutic strategies according to patients’ sex. For each RCT included in the two meta-analyses, firstly, a trial-specific ratio of HRs was calculated from the ratio of the reported HRs in males and in females; secondly, these trial-specific ratios of HRs were combined across trials using a random-effects model to obtain a pooled HRs ratio. A pooled HRs ratio estimate lower than 1 indicates a greater treatment effect in men, and higher than 1 a greater effect in women.
Results : Eight RCTs were included in the first meta-analysis. The pooled OS-HR comparing anti-PD-1/PD-L1 plus chemotherapy versus chemotherapy was 0.76 (95%CI, 0.66-0.87) for men and 0.48 (95%CI, 0.35-0.67) for women. The pooled-ratio of the OS-HRs reported in men versus women was 1.56 (95%CI, 1.21-2.01), indicating a statistically significant greater effect for women. Six RCTs were included in the second meta-analysis: 3 tested an anti-PD-1 alone, while three RCTs tested anti-PD-1/PD-L1 plus chemotherapy. The pooled OS-HRs were 0.78 (95%CI, 0.60-1.00) in men and 0.97 (95%CI, 0.79-1.19) in women for anti-PD-1 alone, compared with 0.76 (95%CI, 0.64-0.91) in men and 0.44 (95%CI, 0.25-0.76) in women for anti-PD-1/PD-L1 plus chemotherapy. The pooled-ratio of OS-HRs, was 0.83 (95%CI, 0.65-1.06) for anti-PD-1 alone, indicating a greater effect in men, and 1.70 (95%CI, 1.16-2.49) for anti-PD-1/PD-L1 plus chemotherapy, indicating a greater effect in women.
Conclusion : Women with advanced lung cancer derived statistically significantly larger benefit from the addition of chemotherapy to anti-PD1/PD-L1 as compared with men.
Journal of the National Cancer Institute , résumé, 2018