Background: While targeted therapies have transformed the treatment landscape of oncogene-addicted non-small cell lung cancer (NSCLC), the influence of sex on treatment outcomes remains insufficiently understood.
Objectives: This systematic review aimed to investigate the impact of sex on clinical outcomes in patients with NSCLC harboring driver fusions treated with targeted therapies enrolled in clinical trials.
Data sources and methods: A comprehensive literature search was conducted using PubMed, Embase, and relevant conference abstracts to identify phase III randomized and early clinical trials that reported sex-specific data, including progression-free survival (PFS), overall survival (OS), overall response rate, and adverse events (AEs), in patients with fusion-positive NSCLC treated with tyrosine kinase inhibitors (TKIs).
Results: This review involved 10 studies reporting PFS data and 3 studies with OS data, focusing on first-line treatments for ALK fusion (9 studies) and RET fusion-positive (1 study) NSCLC. Pooled analysis of hazard ratios (HRs) for PFS and OS in ALK inhibitors trials revealed no significant differences in survival outcomes based on sex. Additionally, none of the studies provided data on sex-based differences in response rates or toxicities, highlighting a significant knowledge gap regarding the impact of sex on secondary outcomes in targeted therapy.
Conclusion: This review found no significant sex-related differences in survival outcomes among patients treated with ALK inhibitors. However, the lack of data on sex-specific response and toxicity emphasizes the need for future research to better understand the role of sex in modulating treatment outcomes and treatment decisions with TKIs.
Keywords: ALK; NSCLC; NTRK; RET; ROS1; gender; oncogenic fusions.
Understanding sex differences in lung cancer treatment outcomes with targeted therapies Why was this review conducted? Lung cancer treatments have advanced significantly with the use of targeted therapies, which are designed to attack specific cancer mutations. However, it is not clear whether a patient's sex influences how well these treatments work. This review looks at whether men and women respond differently to certain targeted treatments for non-small cell lung cancer (NSCLC) to help doctors make better treatment decisions. What did the researchers do? The research team reviewed studies that included both men and women with lung cancer caused by specific genetic changes (called fusion-positive NSCLC). These patients were treated with medications known as tyrosine kinase inhibitors (TKIs), which target cancer-related proteins. The studies were analyzed to see if there were any differences in progression-free survival and overall survival between men and women. What did the researchers find? The review included ten studies looking at how long patients lived without their cancer getting worse and three studies looking at overall survival. These studies focused on patients with two specific genetic changes in their cancer: ALK and RET fusions. The researchers found no major differences between men and women in terms of survival. However, they noted that none of the studies provided information about differences in side effects or how well the cancer responded to treatment between men and women. This is a gap in the research that needs to be addressed. What do the findings mean? This review suggests that, so far, there is no evidence that men and women with NSCLC respond differently to targeted therapies when it comes to survival. However, the lack of data on other important outcomes, like side effects, means that more research is needed to fully understand if sex plays a role in how well these treatments work.
© The Author(s), 2024.