Body Weight Gain Associated with Alectinib in Patients with ALK+ Non-Small Cell Lung Cancer: Pooled Analysis of Individual Patient Data from Four Prospective Clinical Trials

PURPOSEWeight gain is a known adverse event (AE) of alectinib. This study evaluates the progression of actual weight gain over time and explores its association with baseline characteristics.METHODSA pooled analysis of individual patient data from four clinical trials (ALEX, J-ALEX, ALUR, and ML29453) was conducted. Actual weight gain was calculated as the percent change from baseline. A linear mixed model estimated weight change over time and associations between clinical characteristics and weight change.RESULTSFollow-up weights were available for three trials (J-ALEX, ALUR, and ML29453) and missing for ALEX. In total, 2,622 weights were recorded in the first year (N = 302). At baseline, 13.6% of the Japanese population were underweight and 5.0% in the Western population. Actual weight gain of any grade was substantially higher than reported AE rates (49% v 5%), with 18% experiencing ≥10% weight gain (from median 55.6 kg to 64.1 kg). Time on alectinib was positively associated with weight change (β =.37; 95% CI, 0.24 to 0.51; P <.001), corresponding to an average increase of 4.4% over 1 year. Baseline BMI was not associated with weight change in J-ALEX (β = -.090 [95% CI, -0.19 to 0.012]; P =.092) and ALUR/ML29453 (β = -.016 [95% CI, -0.077 to 0.044]; P =.59). Baseline albumin was positively associated with weight change in ALUR/ML29453 (β =.084 [95% CI, 0.027 to 0.14]; P =.0045), although not considered a clinically meaningful predictor.CONCLUSIONWeight gain is under-reported as AE in trials. Actual weights showed ≥10% weight gain in 18% of patients. Clinicians should be aware of this AE, emphasizing the importance of timely identification and monitoring weight. Identifying predictors for weight gain remains challenging.