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: weimi yahoo. : liudanscu qq. Use the link below to share a full-text version of this article with your friends and colleagues. Learn more. 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 patients involved men and 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. 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. Sex difference can potentially affect the immunologic responses to both self and foreign antigens.

Women mount stronger immune response, which could reduce the risk of cancer mortality. A higher smoking prevalence in men increased the tumor mutational burden, which is a strong predictor of benefit from immune checkpoint inhibitors. The studies indicated that the role of sex in ICI trials in cancers were cam4 sex.

How sex associates with ICI efficacy is incompletely elucidated. To address these concerns, we perform the current study of patients to investigate the association of patient sex with the benefits from immune checkpoint inhibitors in NSCLC with recently accumulated evidence.

The main search terms used in the search strategy included immune checkpoint inhibitors anti-programmed cell death 1 or anti-PD-1, anti-programmed cell death ligand 1 or anti-PD-L1, anti-cytotoxic T lymphocyte-associated antigen 4 or anti-CLTA-4specific drug names pembrolizumab, nivolumab, atezolizumab, durvalumab, avelumab, ipilimumab, tremelimumabrandomized controlled trials, lung cancer lung adenocarcinoma, lung squamous cell carcinoma, or NSCLC.

The search strategy is provided in the supplementary materials. To be eligible, randomized controlled trials had to assess the inhibitors of PD-1, PD-L1, CTLA-4, or their combination comparing immunotherapy with other systemic treatment regimens including chemotherapy in patients with lung cancer. Studies that investigated immune checkpoint inhibitors plus chemotherapy compared with chemotherapy alone were also taken into. Eligible studies had to have data available for the hazard ratio HR for overall survival OS or progression-free survival Cam4 sex according to the sex of lung cancer.

Trails that belonged to retrospective or prospective observational cohort studies or reported subgroup analysis for one sex only were excluded.

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Two investigators independently reviewed and extracted the data including first author, publication year, study ID, trial phase, treatment, hazard ratio for overall survival or progression-free survival stratified by patient sex with a standardized data collection form. Any discrepancies or disagreements were discussed and addressed with the consensus of all investigators. A risk of bias assessment was evaluated by using the tool recommended by the Cochrane Collaboration Handbook.

For the Q test, P -value less than 0. Random effects model by DerSimonian-Laird method was applied; otherwise the fixed effects model by Mantel-Haenszel method was performed. We also did subgroup analyses to investigate the variation of effect of sex immunotherapy efficacy. All analysis was performed with Stata version All reported P values were two-sided and P -value less than 0.

A total of potentially related articles were identified from online database by the initial search strategy. After eligibility screening the abstracts and reviewing the full texts, 15 randomized controlled trials RCTs involving patients were finally included in the present study Figure S1.

The main characteristics of the included 15 randomized controlled trials were summarized in Table 1of which were male and were female. All these trials with one phase 2 trail, 14 phase 3 trials were international, multicenter studies published in the past 4 years. Several studies may warrant further explanation due to the cam4 sex des. CheckMate trial was deed to evaluate different nivolumab-based regimens nivolumab monotherapy, nivolumab plus chemotherapy, nivolumab plus ipilimumab versus chemotherapy in distinct patient populations.

The part of CheckMate trial focusing on nivolumab plus ipilimumab versus chemotherapy among patients with NSCLC was identified due to cam4 sex data. Twelve RCTs provided the overall survival data in terms of sex. Heterogeneity was observed among both men and women.

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Subgroup analyses were also performed. All studies were well deed and reported at low risk of sequence generation, incomplete outcome data and selective reporting.

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Several studies were at risk of binding and allocation concealment. Both of which were unlikely to have the influence on the result. The plots suggested the absence of publication bias and sensitivity analysis indicated that the outcome remained consistent Figures S2 and S3. Sex-based differences of the immunologic responses may reflect the different outcome in the efficacy of immune checkpoint inhibitors in male and female.

The aim of the current study is to analyse differences in the response to immunotherapy in both sexes. The result of the current study demonstrated that immune checkpoint inhibitors could improve overall survival and progression-free survival for patients of both sexes in non-small cam4 sex lung cancer.

Interestingly, this study indicated a greater net value of immune checkpoint inhibitors for women HR 0. One possible explanation is that the stronger immune responses from women might lower the risk of cancer mortality. This result seems consistent with Wallis's study male: HR 0. This magnitude of PFS benefit seems clinically relevant.

The study indicated that men treated with PD-1 inhibitor had two-times lower the risk of death than women. Five different meta-analysis have been reported to investigate the efficacy of immune checkpoint inhibitors according to the sex of cancer patients. In the meta-analysis of Wu and colleagues, 33 subgroup analysis by type of cancer, four trails of NSCLC including patients showed that men had the better survival benefit compared with women. The current study included an updated search of the largest of patients patients from 15 RCTs with relatively complete immunotherapy agents, of which increased the credibility of our analysis.

A meta-analysis cam4 sex that PD-1 inhibitors for men would consequently have better OS benefit than women. A preclinical study hypothesized that PD-L1 inhibitors for women would become more efficacious consequently compared to men. From this point of view, there was a ificantly higher magnitude of anti-PD-1 and anti-PD-L1 efficacy in men.

Grassadonia et al demonstrated that CTLA-4 inhibitors tended to improve the survival in male patients but not in female patients. One possible explanation is that their mechanisms are different. Therefore, further studies with functional analysis are warranted to cam4 sex the issue. Preclinical studies showed that conventional therapy including the radiotherapy and chemotherapy could kill tumor cells and induce PD-L1 expression on tumor cells. From all the subgroups, we could conclude that efficacy of immune checkpoint inhibitors may not be equally effective according to sex and ICI may seem more beneficial in men of NSCLC patients.

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To the best of our knowledge, we speculate on three possible reasons that could explain the difference between men and women. First, sex dimorphism in immunity indicates that the stronger immune responses occurring in women could lower the risk of cancer mortality and higher incidence of autoimmune diseases also could make them more susceptible to produce ICI-related adverse events causing higher possibility of treatment discontinuation.

Second, gender dimorphism in behaviors such as higher smoking frequency in men, which increases tumor mutational burden TMB greatly and such correlates with immune checkpoint inhibitor efficacy. Third, lower smoking prevalence with lower tumor immunogenic landscape and higher EGFR mutation might lead to these among women patients with lung cancer, and those female patients with EGFR tumor mutations receive no survival benefit from the immune checkpoint inhibitors.

We performed a systematic review and meta-analysis to investigate the efficacy of immunotherapy in lung cancer according to sex and demonstrated that male patients could derive larger relative survival benefit from immune checkpoint inhibitors compared with available standard therapies then female patients. The present study had several limitations.

Second, several RCTs of immune checkpoint inhibitors excluded due to lack of available sex-subgroup analysis data that might indicate sex differences if included in the analysis. Fourth, differences from between both male and female patients cam4 sex be attributed to other factors such as prevalence of autoimmune diseases, difference in the of both men and women, and difference of life style.

The above limitations may have a certain influence on the final outcome. Despite the limitations, the current study is the largest meta-analysis incorporating outcomes from 15 RCTs involved over patients in NSCLC, providing the increased credibility of. In the current study, immune checkpoint inhibitors are ificantly cam4 sex with prolonged overall survival and prolonged progression-free survival in both male and female patients in NSCLC.

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Prospective randomized controlled trials of greater inclusion of women stratified by sex and deeper understanding of molecular mechanisms of tumor immune response and response are needed to validate the difference of efficacy of immunotherapy in male and female patients in NSCLC. Weimin Li and Dan Liu contributed to conceptualization and supervision. All the authors approved the final version. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors.

Any queries other than missing content should cam4 sex directed to the corresponding author for the article. Volume 8Issue 8. The full text of this article hosted at iucr. Please check your for instructions on resetting your password. If the address matches an existing you will receive an with instructions to retrieve your username. Cancer Medicine. Chengdi Wangorcid. Corresponding Author liudanscu qq. Corresponding Author weimi yahoo. First published: 04 June Chengdi Wang and Wenliang Qiao are contributed equally to this work. Tools Request permission Export citation Add to favorites Track citation.

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