Let's talk about sex: Survival among females and males in a real‐world cohort treated with pembrolizumab for non‐small cell lung cancer

Innate differences in the female and male immune systems and subgroup results from clinical trials have led researchers to hypothesize there could be sex-based disparities in the effectiveness of immune checkpoint inhibitors for anticancer treatment. This real-world study evaluated potential sex-based disparities in survival among non-small cell lung cancer (NSCLC) patients treated with pembrolizumab as monotherapy or in combination with chemotherapy. The population-based cohort included 1586 females and 1978 males diagnosed with advanced NSCLC in Norway, treated with first-line pembrolizumab (2017-2021) or platinum-based chemotherapy (2012-2016). Sex-based survival differences among pembrolizumab users, and survival benefits relative to chemotherapy users, were evaluated using lung-cancer specific survival adjusted for age, stage, histology, cardiovascular disease, education, and income. Results were presented for pembrolizumab mono- and combination therapy separately. We did not observe sex-based differences in survival among pembrolizumab monotherapy users. Among combination therapy users, females had higher survival than males (7 percentage points higher 18 months after treatment initiation); this effect persisted until the end of follow-up (36 months). When comparing the effect of pembrolizumab relative to chemotherapy, males derived a larger survival benefit from monotherapy than females. We did not observe any sex-based disparities in the survival benefit of combination therapy. Sex-based survival disparities in our study appeared to be associated with disparities in the effectiveness of chemotherapy, but could also indicate that pembrolizumab monotherapy is more effective for males. Framing the sex-based effectiveness of pembrolizumab as a survival difference versus benefit relative to chemotherapy affected whether a disparity was observed.