Effect of sex on the efficacy of patients receiving immune checkpoint inhibitors in advanced non‐small cell lung cancer

Abstract

Immune checkpoint inhibitors (ICIs) have shown promising efficacy in the treatment of non‐small cell lung cancer (NSCLC). Sex‐associated dimorphism in immune system response is acknowledged, but the effect of patients’ sex on efficacy of ICIs as treatment in NSCLC still remains controversial. The present study was conducted to investigate the difference in efficacy of NSCLC patients receiving immune checkpoint inhibitors according to the sex. A total of 9583 patients involved 6567 men and 3016 women with advanced lung cancer from 15 randomized controlled trials were included in this study. An overall survival (OS) benefit of immune checkpoint inhibitors was illustrated in both male (HR 0.76, 95% CI 0.71‐0.82) and female (HR 0.73, 95% CI 0.58‐0.91) patients, and a progression‐free survival (PFS) benefit was also found in both men (HR 0.67, 95% CI 0.58‐0.77) and women (HR 0.73, 95% CI 0.56‐0.95) in NSCLC. Both PD‐1/PD‐L1 inhibitors alone and PD‐1/PD‐L1 plus chemotherapy significantly improved the OS and PFS in male patients. Whereas in females, PD‐1 inhibitors or monotherapy significantly benefited the OS but not the PFS, PD‐L1 inhibitors or combination therapy significantly prolonged the PFS but not the OS. No survival benefit was found in both male and female patients from the CTLA‐4 inhibitors. The current study indicated that the magnitude of survival benefit is sex‐dependent and male patients seemed to obtain more consistent and favorable outcomes from ICIs than women patients in NSCLC.

An evaluation of self-perceived knowledge, attitudes and behaviours of UK oncologists about LGBTQ+ patients with cancer

“…17 18 Of note, there is also increasing evidence of the importance of sex assigned at birth as a marker of prognosis, adverse events and response to treatment in non-sexrelated cancers. [19][20][21][22] A recent European Society for Medical Oncology (ESMO) report 23 recommended that 'men and women with non-sex-related cancers should no longer be considered as subgroups, but as biologically distinct groups of patients'. This raises clinical questions for the treatment of trans patients, which need to be answered in order to provide optimal care.…”

Sex Differences and Adverse Effects between Chemotherapy and Immunotherapy for Non-Small Cell Lung Cancer

“…The tyrosine kinase inhibitors have pneumonitis, esophagitis and skin rash which is associated in most cases with the dosage [14,15]. Immunotherapy has orogonitis, pneumonitis, athritis, vitiligo, resurgence of hepatitis and disregulation of the thyroid gland [6,16] An aspect that has not been fully investigated is the differences of adverse effects, gender and disease response between chemotherapy and immunotherapy [17][18][19][20][21]. In the current research paper we investigated the differences of adverse effects between chemotherapy and immunotherapy in first line treatment for squamous cell carcinoma.…”

Functional signatures in non-small-cell lung cancer: a systematic review and meta-analysis of sex-based differences in transcriptomic studies

“…Of note, sex-based immunological differences in lung adenocarcinoma might have an impact on immunotherapy response. Different studies have addressed the role of sex in immunotherapy [40,[51][52][53] , establishing improved survival for female NSCLC patients. The discovered molecular pathways differentially activated between male and female lung adenocarcinoma patients may underlie phenotypic differences regarding immunotherapy response.…”