Men and Women May Respond Differently to Immunotherapy for NSCLC

Women with advanced non-small cell lung cancer (NSCLC) may benefit more from the combination of chemotherapy plus PD-1/PD-L1 inhibitors compared with men, according to the results of 2 meta-analyses.¹

Previous research has indicated that men may derive more benefit from anti-CTLA-4 or anti-PD-1 treatment than women do. In these current meta-analyses, researchers looked at whether women could experience a greater benefit than men from treatment with chemotherapy and anti-PD-1/PD-L1 therapy.

In the first study, the researchers looked at 8 randomized clinical trials that tested PD-1/PD-L1 blockade plus chemotherapy compared with chemotherapy alone.

Results indicated that women derived more benefit from this therapeutic combination, and had an overall survival hazard ratio of 0.48 (95% CI, 0.35-0.67) compared with 0.76 (95% CI, 0.66-0.87) for men. A pooled ratio of the overall survival hazard ratios in men compared with women was 1.56, which the researchers wrote indicated “a statistically significant greater effect for women.”

In the second meta-analysis, the investigators looked at 6 randomized clinical trials of first-line systemic treatment in advanced NSCLC testing anti-PD-1/PD-L1 monotherapy or in combination with chemotherapy. Three trials tested monotherapy and three studies tested combination therapy.

The pooled overall survival hazard ratios for combination treatment was 0.44 (95% CI, 0.25-0.76) for women compared with 0.76 for men (95% CI, 0.64-0.91). In comparison, looking at monotherapy (either chemotherapy or anti–PD-1 therapy), the hazard ratio was 0.97 (95% CI, 0.79-1.19) for women and 0.78 (95% CI, 0.60-1.01) for men. Again, the pooled ratio of overall survival hazard ratios for combined therapy indicated a greater effect for women (1.70; 95% CI, 1.16-2.49).

According to the researchers, these results are hypothesis-generating only and must be further validated.

“However, data reported here and in our previous work, support the need for different therapeutic strategies to be tested in male and female populations to further improve the use of immunotherapy,” they wrote.

Reference

1. Conforti F, Pala L, Bagnardi V, et al. Sex-based heterogeneity in response to lung cancer immunotherapy: a systematic review and meta-analysis [published online May 20, 2019].  J Natl Cancer Inst. doi: 10.1093/jnci/djz094