Abstract 1036P
Background
This study investigated the role of programmed death-ligand 1 (PD-L1) expression in the sex-related differences in immune checkpoint inhibitor (ICI) efficacy.
Methods
We first pooled individual patient-level data from prospective clinical trials to evaluate ICI efficacy between male and female stratified by PD-L1 expression. We further combined individual patient-level data with meta-analysis of randomized controlled trials (RCTs) to assess the efficacy of ICI versus chemotherapy in each of the sexes. Finally, we assessed sex associated with landscape of tumor microenvironment among PD-L1 expression-negative patients.
Results
In total, 1,594 patients were included from five clinical trials, and nine RCTs with 4,718 patients were included in meta-analysis. Among patients with PD-L1 expression<1%, individual patient-level analysis showed that overall survival (OS) with ICI was significantly longer for female compared with male (HR 0.58, 95% CI 0.42-0.80; P<.001). The OS benefit of ICI over chemotherapy was significantly different in female (HR 0.57, 95% CI 0.38-0.85; P=.006), but not in male. Among patients with PD-L1 expression≥1%, individual patient-level analysis combined with meta-analysis showed that the OS benefit of ICI over chemotherapy was significantly different in male (HR 0.76, 95% CI 0.67-0.85; P<.01), both in first-line patients (HR 0.79, 95% CI 0.65-0.97; P=0.02) and subsequent-line patients (HR 0.73, 95% CI 0.62-0.85; P<.01); however, this benefit for female was only significant in subsequent-line patients (HR 0.77, 95% CI 0.62-0.96; P=.02). Additionally, the central memory T cell was potentially correlated with the OS differences between the sexes at PD-L1 expression<1%.
Conclusions
The association of sex with OS benefits of ICIs in cancer were greatly influenced by PD-L1 expression. At PD-L1 expression<1%, ICI should be recommended for female but not for male. At PD-L1 expression≥1%, ICI should be recommended for male regardless of treatment lines; whereas for female, ICI could be only recommended in subsequent-line setting. Sex and PD-L1 expression should be jointly considered in the clinical decision making for ICI in cancer.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Herui Yao.
Funding
Has not received any funding.
Disclosure
Herui Yao: Grants: The National Science and Technology Major Project (2020ZX09201021), The Medical Artificial Intelligence Project of Sun Yat-Sen Memorial Hospital (YXRGZN201902), The National Natural Science Foundation of China (81572596, 81972471, U1601223), The Natural Science Foundation of Guangdong Province (2017A030313828), The Guangzhou Science and Technology Major Program (201704020131), The Guangdong Science and Technology Department (2017B030314026), The Sun Yat-sen University Clinical Research 5010 Program (2018007), The Sun Yat-sen Clinical Research Cultivating Program (SYS-C-201801). Anlin Li: Funds: The Cultivation of Guangdong College Students’ Scientific and Technological Innovation (pdjh2019a0212). All other authors have declared no conflicts of interest.