Meta-Analysis Exploring Tyrosine Kinase Inhibitor-Induced Weight Gain in Oncogene-Addicted NSCLC

For patients with oncogene-addicted NSCLC treated with tyrosine kinase inhibitors (TKIs), weight gain has recently gained attention as a frequent treatment-related effect. Identifying those TKIs more frequently associated with weight gain is crucial for further characterizing body composition-related modifications, deepening their metabolic impact, and guiding treatment decisions, considering the potential influence of weight gain on patients' quality of life and long-term outcomes.

A systematic search was conducted across PubMed, Scopus, Cochrane, and meeting resources. A meta-analysis was conducted to quantify the magnitude of weight gain, and meta-regression was applied to explore the association between this side effect, and demographic and clinical parameters.

Among 7596 identified studies from January 2009 to December 2024, 18 pivotal trials reporting weight gain data were included in the final analysis, encompassing a total of 25 arms. Lorlatinib revealed the highest risk of treatment-induced weight gain [incidence 36%; 95% confidence interval (CI): 26%-46%; I² = 92%], followed by alectinib [incidence 15%; 95% CI: 12%-18%; I² = 52%] and crizotinib [incidence 5%; 95% CI: 0%-13%; I² = 93%]. Osimertinib and erlotinib indicated the lowest incidence of weight gain. The meta-regression revealed no significant correlation among weight gain, sex, age, and performance status, thus suggesting a drug-specific effect.

Our findings confirmed the unique profile of lorlatinib regarding weight gain, regardless of patient characteristics. Considering the impressive prognostic horizons achievable with TKIs in oncogene-addicted NSCLC, adequate reporting in clinical trials, assessment and monitoring of weight gain, body composition modifications, and impact on quality of life should be prioritized, together with adequate lifestyle-based strategies for its management.