Weight, BSA, Toxicity, and Efficacy of Tyrosine Kinase Inhibitors for Mutated NSCLC.

[INTRODUCTION] ALK tyrosine kinase inhibitors (ALK TKIs) are started at a standard dose regardless of patients' weight and body surface area (BSA). In this retrospective analysis, the authors explored whether body size variables were associated with toxicity and efficacy.

[METHODS] Retrospective data for positive patients at the Princess Margaret Cancer Centre were extracted from electronic health records. Associations between BSA/weight quartiles and dose reductions (DRs), temporary interruptions (TIs), and permanent discontinuation due to toxicity were evaluated using generalized linear mixed modeling. Survival analysis was conducted using Kaplan-Meier curves and log-rank tests.

[RESULTS] Among 142 patients with -positive NSCLC treated between July 2012 and March 2024, the median age was 58 years, 54% were female, 78% never-smokers, 49% were Asian, and 37% were Caucasian. A significantly higher proportion of males were in the highest BSA Q4 (89%, < 0.001), whereas more females (91%, < 0.001) and Asians were in the lowest BSA Q1 (80%, < 0.001).Higher weight at ALK TKI initiation was associated with an increased likelihood of DR at any time (adjusted odds ratio [aOR] = 1.20 per 10-kg increase, 95% confidence interval: 1.0-1.4, 0.04), as was having higher BSA (aOR = 2.00 per 0.5-U increase, 95% confidence interval: 1.0-3.9, 0.04). TIs were associated with higher weight (10-kg increase, aOR = 1.28, 0.006), BMI (5-U BMI increase, aOR = 1.40, 0.02), and BSA (0.5-U increase, aOR = 2.59, 0.005). These weight/BSA results were statistically significant in patients during alectinib or lorlatinib treatment. In contrast, permanent discontinuation was associated with higher weight/BSA in brigatinib/ceritinib/crizotinib-treated patients. In multivariable analysis, older age and male sex were independently associated with more DRs and TIs. Weight and BSA quartiles were not associated with progression-free survival ( 0.4) or overall survival ( 0.6).

[CONCLUSIONS] Higher weight and larger BSA at the start of ALK TKI treatment were associated with higher likelihood of toxicity, leading to more DRs and TIs-particularly in males and patients receiving alectinib and lorlatinib. However, weight and BSA were not associated with treatment outcomes.