Predictive value of weight and BSA in assessing toxicity during ALK-TKIs in non-small cell lung cancer

Background ALK tyrosine kinase inhibitors (ALK TKi) are an essential treatment with excellent results in survival and QoL. Unlike chemotherapy, ALK-TKis are started at a standard dose regardless of patients’ weight and body surface area (BSA). To explore whether body size variables might affect toxicity and efficacy, we undertook this retrospective analysis to determine the influence of weight and BSA on treatment toxicity (TT), need for dose adjustment and outcomes.MethodsClinic-demographic, ALK-TKIs, toxicity and outcomes were collected from electronic medical charts. Weight and BSA at treatment initiation for each ALK-TKI were divided into quartiles (Q1-Q4) and correlated with toxicity, dose modifications (DM) and outcomes.ResultsOf 147 ALK-positive NSCLC patients seen between July 2012- March 2024, the median age was 57.2 years; 80 (55%) were female; 115 (79%) never-smoker; 73 (50%) Asian and 54 (37%) Caucasian. There were differences in BSA between sex and ethnicity, with more males in the highest BSA Q4 (14% vs 86%, p<0.001), and more females (92% vs 8%, p<0.001) and Asians in the lowest BSA Q1 (81% vs 8% Caucasian, p<0.001). Weight at start of ALK-TKi was associated with significant differences in DM at any time (aOR= 1.18 per 0.5-unit increase, 95% CI 1.01-1.38, p=0.039), as was BSA (aOR 1.80, 95% CI 1.00-3.21, p=0.048). Lower dose intensity (DI) during TKi therapy (0-100% of total dose), was associated with higher weight (p<0.001) and higher BSA (p=<0.001). Treatment discontinuation was associated with lower weight and BSA for temporary discontinuation (TD) (weight aOR 1.23, p=0.007, and BSA aOR=2.15, p=0.008), and non-significant trends for permanent discontinuation (PD) (weight aOR=1.24, p=0.012, and BSA aOR=2.28, p=0.11). There was no correlation between DM or TD based on the line or individual ALK-TKi administered. Interestingly, in the adjusted analysis, age and sex also were associated with DM, DI, and TD. Despite differences in the need for DM, weight and BSA were not negatively associated with PFS (p=0.3) or overall survival (p=0.8).ConclusionsWeight and BSA may provide an opportunity to identify patients at higher risk for ALK-TKi related-toxicity requiring DM and TD. However, this did not negatively impact treatment outcomes.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest.