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

Abstract

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.

Outcome differences by sex in oncology clinical trials

“…Previous reports of improved SOR for females in NHL/rituximab were generated from single trials or anecdotal evidence collected from a few trials 56 , but the sex-preference in response to rituximab has not been systematically reported across trials. Importantly, other anecdotal reports of sex differences for various malignancy/treatment combinations 25 , 31 , 57 , 58 are not supported by our analysis of all oncology trials. Notably, rituximab does not show consistently better outcomes in females across other B-cell disorders 59 , suggesting that oncology clinical trials may reflect an interaction of NHL and rituximab with sex specificity, rather than a sex-specific pharmacodynamic property 60 .…”

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.…”

Immunotherapy in Elderly Patients Affected by Non-Small Cell Lung Cancer: A Narrative Review

“…Data from single-agent ICIs studies are disappointing, but globally it seems that ICIs may result more effectively in men than women; perhaps because tumours in men are potentially more immunogenic given a higher mutational burden [178]. Conversely, a systematic review and meta-analysis of randomized clinical trials showed that a greater improvement in OS and PFS was observed in female patients than in male patients with combination chemoimmunotherapy as a first-line therapy [179]. However, available evidence is not strong enough to influence treatment choices; an insufficient number of studies analyze data by sex in a prospective and pre-planned manner.…”