The impact of gender on The efficacy of immune checkpoint inhibitors in cancer patients: The MOUSEION-01 study

Santoni, Matteo; Rizzo, Alessandro; Mollica, Veronica; Matrana, Marc; Rosellini, Matteo; Faloppi, Luca; Marchetti, Andrea; Battelli, Nicola; Massari, Francesco

doi:10.1016/j.critrevonc.2022.103596

Cited by 130 publications

(85 citation statements)

References 65 publications

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“…Many recent studies, including meta-analyses, have reported the association between sex and the efficacy of ICIs in NSCLC based on the following observations [ 2 – 4 , 12 , 19 , 23 , 24 , 26 , 29 – 31 ] (1) Faster clearance of pathogens and greater vaccine effectiveness are observed in females compared with males [ 11 , 28 ] (2) Females have higher rates of autoimmune disorders compared with males [ 11 , 28 ]. These findings indicate that females might exhibit greater immunologic responses to antigens than males, and there might be a difference in the efficacy of ICIs between females and males.…”

Section: Introductionmentioning

confidence: 99%

Association between sex and outcomes in patients with non-small-cell lung cancer receiving combination chemoimmunotherapy as a first-line therapy: a systematic review and meta-analysis of randomized clinical trials

et al. 2022

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Introduction Recently, several meta-analyses have investigated the association between sex and the efficacy of immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC). However, this issue remains controversial, because the results have been inconsistent. Moreover, the effect of sex on outcomes in patients with NSCLC receiving combination chemoimmunotherapy as a first-line therapy is poorly understood. The aim of this study was to examine the association between sex and outcomes in patients with NSCLC receiving combination chemoimmunotherapy as a first-line therapy. Methods We searched PubMed and Scopus from database inception to Feb 18, 2022 and performed a systematic review and meta-analysis of randomized and controlled clinical trials investigating ICI+non-ICI vs non-ICI as a first-line therapy in NSCLC. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS) in male and female patients were calculated using common and random-effects models. Results We analyzed 5,830 patients, comprising 4,137 (71.0%) males and 1,693 (29.0%) females, from nine randomized clinical trials. The pooled HR (95%CI) for OS comparing ICI+non-ICI vs non-ICI was 0.80 (0.72–0.87) for males and 0.69 (0.54–0.89) for females. The pooled HR (95%CI) for PFS comparing ICI+non-ICI vs non-ICI was 0.60 (0.55–0.66) for males and 0.56 (0.44–0.70) for females. Conclusions In patients with NSCLC receiving combination chemoimmunotherapy as a first-line therapy, a greater improvement in OS and PFS was observed in female patients than in male patients.

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Section: Introductionmentioning

confidence: 99%

Association between sex and outcomes in patients with non-small-cell lung cancer receiving combination chemoimmunotherapy as a first-line therapy: a systematic review and meta-analysis of randomized clinical trials

et al. 2022

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“…As both pathways are targetable with available therapeutics [27,28], it is interesting to consider how the TSI approach might inform stratification for treatment. As an illustration, clinical experience indicates that females exhibit a smaller survival benefit from immune checkpoint inhibition (ICI) than males [29][30][31]. Thus, it would be reasonable to hypothesize that the immune signature associated with the lowest TSI values is one of resistance to ICI.…”

Section: Discussionmentioning

confidence: 99%

Accounting for sex differences variability in the design of sex-adapted cancer treatments

Yang

Rubin

2023

Preprint

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The significant sex differences that exist in cancer mechanisms, incidence, and survival, have yet to impact clinical practice. We hypothesized that one barrier to translation is that sex differences in cancer phenotypes resemble sex differences in height: highly overlapping, but distinct, male and female population distributions that vary continuously between female- and male- biased extremes. A consequence of this variance is that sex-specific treatments are rendered unrealistic, and our translational goal should be adaptation of treatment to the unique mix of sex-biased mechanisms that are present in each patient. To develop a tool that could advance this goal, we applied a Bayesian Nearest Neighbor (BNN) analysis to 8370 cancer transcriptomes from 26 different adult and 4 different pediatric cancer types to establish patient-specific Transcriptomic Sex Indices (TSI). TSI precisely partitions an individual patients whole transcriptome into female- and male- biased components such that cancer type, patient sex, and transcriptomics, provide a novel and patient-specific mechanistic identifier that can be used for sex-adapted, precision cancer treatment planning.

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“…However, findings appear inconsistent depending on patient demographics and tumour type [ 37 , 39 ]. The recent report of findings from the MOUSEION-01 study comparing the effectiveness of checkpoint inhibitors across multiple cancer types showed a significant and reduced overall effect of therapy in females [ 102 ]. CSCC was not included in the series of trials reviewed.…”

Section: Discussionmentioning

confidence: 99%

Sex Disparity for Patients with Cutaneous Squamous Cell Carcinoma of the Head and Neck: A Systematic Review

Tan

Seth

Fischer

et al. 2022

Cancers

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The incidence of head and neck cutaneous squamous cell carcinoma (HNcSCC) is unevenly distributed between men and women. At present, the mechanism behind this disparity remains elusive. This study conducted a systematic review and meta-analysis of proportions to investigate the disparity between sexes for patients with HNcSCC. PubMed, Scopus, EMBASE, MEDLINE, Emcare and CINAHL were searched in November 2021 and June 2022 (N > 50, English, human), and studies which examined the association between sex and HNcSCC were included. Analysis was conducted using RStudio with data and forest plots displaying males as a proportion of total patients with HNcSCC. Two independent researchers performed study selection, data extraction, data analysis and risk of bias. Eighty-two studies (1948 to 2018) comprising approximately 186,000 participants (67% male, 33% female) from 29 countries were included. Significantly more males had HNcSCC overall (71%; CI: 67–74). Males were also significantly more affected by cSCC of the ear (92%; CI: 89–94), lip (74%; CI: 66–81), and eyelid (56%; CI: 51–62). This study found HNcSCC disproportionately affected males overall and across all subtypes. Improving our understanding of sex-specific mechanisms in HNcSCC will better inform our preventive, therapeutic and prognostic practices.

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The impact of gender on The efficacy of immune checkpoint inhibitors in cancer patients: The MOUSEION-01 study

Cited by 130 publications

References 65 publications

Association between sex and outcomes in patients with non-small-cell lung cancer receiving combination chemoimmunotherapy as a first-line therapy: a systematic review and meta-analysis of randomized clinical trials

Association between sex and outcomes in patients with non-small-cell lung cancer receiving combination chemoimmunotherapy as a first-line therapy: a systematic review and meta-analysis of randomized clinical trials

Accounting for sex differences variability in the design of sex-adapted cancer treatments

Sex Disparity for Patients with Cutaneous Squamous Cell Carcinoma of the Head and Neck: A Systematic Review

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