Background: Immunotherapy with ICIs has revolutionized the treatment for NSCLC. The impact of sex on treatment outcomes remains unclear. The aim of this study was to evaluate sex-related differences in immunotherapy outcomes in a real-world population of NSCLC patients. Methods: Demographics, clinical, pathological characteristics, and treatment-related variables were analyzed to understand the differences in efficacy and safety outcomes in relation to sex. Results: 174 advanced NSCLC patients receiving first-line ICIs, either alone or in conjunction with chemotherapy, were included. No differences based on gender were observed in PFS and OS. Prognostic factors for OS and PFS included liver metastases and CRP levels at treatment discontinuation (TD). IrAE-related TD occurred at a significantly higher rate in females. GI toxicity, including hepatitis and colitis, was predominantly observed in females, whereas pneumonitis was the most frequent irAE leading to TD in males. Conclusions: Despite no significant differences based on gender being observed in survival outcomes, our study showed that female patients with advanced NSCLC receiving ICIs are at a substantially greater risk of severe symptomatic irAEs and TD. This finding indicates that broad-based sex differences could potentially exist and emphasizes the need for further investigations into the role played by gender in immunity and cancer immunotherapy treatment.

Antibody–drug conjugates (ADCs) represent an emerging class of targeted anticancer agents that have demonstrated impressive efficacy in numerous cancer types. In non-small cell lung cancer (NSCLC), ADCs have become a component of the treatment armamentarium for a subset of patients with metastatic disease. Emerging data suggest that some ADCs exhibit impressive activity even in central nervous system (CNS) metastases, a disease site that is difficult to treat and associated with poor prognosis. Herein, we describe and summarize the existing evidence surrounding ADCs in NSCLC with a focus on CNS activity.

Objective: Immune checkpoint inhibitors (ICIs) are front-line treatment options for NSCLC. ICI therapy is associated with a risk of immune-related adverse events (irAEs). Checkpoint inhibitor pneumonitis (CIP) is a potentially life-threatening irAE. Previous studies have demonstrated that asthma and interstitial lung disease are associated with an increased risk of CIP. We sought to determine whether chronic obstructive pulmonary disease (COPD) is associated with CIP. Methods: This retrospective study examines a cohort of ICI-treated NSCLC patients either with or without chemotherapy at the Anna and Peter Brojde Lung Cancer Centre, Jewish General Hospital in Montreal, Canada between 2014 and 2023. We explored associations between risk factors and CIP using the Mann–Whitney U test or Fisher’s exact test. Analysis of prognostic factors was performed using a logistic regression model. All statistical analyses were carried out using SPSS software, version 24.0 (SPSS, Chicago, IL, USA). p-values of 0.05 or less were considered significant. Results: Of the 327 selected patients on ICIs, 23 experienced an acute respiratory deterioration that was attributed to CIP, 87/327(26.6%) patients had a pre-existing diagnosis of COPD, and 11/87 (12.6%) COPD patients experienced CIP compared to 13/240 (5.5%) non-COPD patients (p = 0.061). There was no statistical or clinically meaningful correlation between COPD severity and CIP. The only variable significantly associated with CIP was a poor ECOG performance status. Among ECOG 1 patients, 18/91 (19.8%) experienced CIP compared to 5/226 (2.2%) of those with an ECOG of 0. A multivariate assessment involving all 327 patients revealed no significant factors affecting CIP development. Conclusions: Our single-institution study revealed that although there was a trend, the presence of COPD was not statistically associated with an increased risk of CIP. Additionally, neither FEV1 nor DLCO had a meaningful impact on the development of CIP in COPD patients. Given these findings, we emphasize the need for larger prospective studies to confirm these observations before drawing definitive clinical recommendations.