Sex difference in response to non-small cell lung cancer immunotherapy: an updated meta-analysis

Abstract

Background Studying sex differences in the efficacy of immunotherapy may contribute to the practice of the precision medicine, especially in non-small cell lung cancer (NSCLC), a kind of cancer with sexual bimorphism. Methods Published randomized controlled trials (RCTs), published by PubMed, Medline, Embase, and Scopus, before 15 June 2022, testing immunotherapy (CTLA-4 or PD-1/L1 inhibitor alone, combination or with chemotherapy) versus non-immunotherapy (receiving chemotherapy or placebo only) were included to assess different efficacy between males and females. The primary endpoint was overall survival (OS). This meta-analysis was registered with PROSPERO (CRD42022298439). Results Sixteen RCTs, involving 10,155 patients with advanced NSCLC, was collected in this meta-analysis. The pooled HR comparing immunotherapy vs non-immunotherapy were 0.76 (95%CI 0.71–0.81) for males and 0.74 (95%CI 0.63–0.87) for females. The pooled HRs comparing immune-checkpoint inhibitors (ICIs) plus chemotherapy versus chemotherapy were 0.79 (95%CI 0.70–0.89) for males and 0.63 (95%CI 0.42–0.92) for females. The pooled HRs comparing ICIs versus chemotherapy were 0.74 (95%CI 0.67–0.81) for males and 0.83 (95%CI 0.73–0.95) for females. In squamous NSCLC, the pooled HRs comparing immunotherapy vs non-immunotherapy were 0.73 (95%CI 0.58–0.91) for males and 0.74 (95%CI 0.37–1.48) for females. In non-squamous NSCLC, the pooled HRs comparing immunotherapy versus non-immunotherapy were 0.62 (95%CI 0.71–0.94) for males and 0.59 (95%CI 0.39–0.89) for females. Conclusion Compared to chemotherapy, immunotherapy can improve the prognosis of patients with advanced NSCLC. Meanwhile, there are sex differences in the efficacy of immunotherapy. KEY MESSAGE Compared to chemotherapy, immunotherapy can improve the prognosis of patients with advanced NSCLC. The most interesting thing in this study is that immunotherapy showed significant sex differences in the treatment of squamous NSCLC.

Sex Differences in Lung Cancer

“…In the NSCLC cohort of another meta-analysis carried out by Grassadonia et al, PFS was higher in immunotherapy-treated males than in females, and anti-CTLA-4 treatment was associated with longer OS in males [ 117 ]. Similar results were also observed Laing et al in a more recent meta-analysis [ 118 ]. In contrast, a meta-analysis carried out by Conforti et al showed longer OS in women than in men treated with ICBs; however, this study excluded a large number of female patients from their final analysis, making interpretation of the results difficult [ 119 ].…”

Sex‐based immune microenvironmental feature heterogeneity in response to PD‐1 blockade in combination with chemotherapy for patients with untreated advanced non‐small‐cell lung cancer

“…21 More recently, several update meta-analyses also reported that female patients had a greater treatment outcomes improvement than male patients. [22][23][24] Consistently, this study analyzed 175 patients with untreated advanced or metastatic NSCLC received PD-1 blockade plus chemotherapy or chemotherapy and also observed that female patients derived a larger benefit from first-line PD-1 blockade in combination with chemotherapy, but not chemotherapy, than male patients. Taken together, these findings suggest that female patients with untreated advanced or metastatic NSCLC could derive a larger benefit from PD-1 blockade plus chemotherapy.…”

Role of sex and sex hormones in PD-L1 expression in NSCLC: clinical and therapeutic implications

“…Otherwise, women experienced increased survival rates, in chemoimmunotherapy ( 34 ). Additionally, the pooled HRs comparing ICIs vs chemotherapy were 0.74 (95% CI0.67-0.81) for men and 0.83 (95% CI 0.73-0.95) for women ( 35 ). Better PFS was also observed in advanced NSCLC male patients treated with ICI (5 months vs 4).…”