Analysis of significant weight gain in patients using alectinib for ALK-positive lung cancer.

person Barend Joël Sikkema Erasmus MC, Rotterdam, Netherlands info_outline Barend Joël Sikkema, Simon de Leeuw, Melinda Pruis, Mostafa Mohseni, Geerten Dieuwert Marijn Veerman, Marthe Paats, Daphne W Dumoulin, Egbert F. Smit, Annemie M.W.J. Schols, Ron H.J. Mathijssen, Elisabeth Van Rossum, Anne-Marie C. Dingemans

Authors person Barend Joël Sikkema Erasmus MC, Rotterdam, Netherlands info_outline Barend Joël Sikkema, Simon de Leeuw, Melinda Pruis, Mostafa Mohseni, Geerten Dieuwert Marijn Veerman, Marthe Paats, Daphne W Dumoulin, Egbert F. Smit, Annemie M.W.J. Schols, Ron H.J. Mathijssen, Elisabeth Van Rossum, Anne-Marie C. Dingemans Organizations Erasmus MC, Rotterdam, Netherlands, Erasmus MC University Medical Center, Rotterdam, Netherlands, Erasmus Medical Center, Rotterdam, Netherlands, Erasmus MC Kankerinstituut, Rotterdam, Netherlands, Department of Pulmonary Medicine, Erasmus MC Rotterdam, Rotterdam, Netherlands, Department of Pulmonary Diseases, Leiden University Medical Centre, Leiden, Netherlands, Maastricht University, Maastricht, Netherlands, Erasmus MC - Kanker Instituut locatie Danïel den Hoed, Rotterdam, Netherlands, Department of Pulmonology, Erasmus University Medical Center, Rotterdam, Netherlands Abstract Disclosures Research Funding No funding received None. Background: Alectinib is standard of care for metastatic anaplastic lymphoma kinase positive (ALK+) nonsmall cell lung cancer (NSCLC). Weight gain is an unexplored side effect reported in ~10%. To prevent or intervene alectinib-induced weight gain, more insight in its extent and etiology is needed. Methods: Change in body composition was analyzed in a prospective series of 46 patients with ALK+ NSCLC, treated with alectinib. Waist circumference, skeletal muscle (SM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were quantified using sliceOmatic software on computed tomography (CT) images at baseline, three months (3M) and one year (1Y). To investigate an exposure-toxicity relationship, alectinib plasma concentrations were quantified. Four patients with > 10 kg weight gain were referred to Erasmus MC Obesity Center for in-depth analysis (dietary habits, metabolic/endocrine assessment). Results: Mean increase in waist circumference was 9 cm (9.7%, p < 0.001) in 1Y with a 40% increase in abdominal obesity (p = 0.014). VAT increased 10.8 cm2 (15.0%, p = 0.003) in 3M and 35.7 cm2 (39.0%, p < 0.001) in 1Y. SAT increased 18.8 cm2 (12.4%, p < 0.001) in 3M and 45.4 cm2 (33.3%, p < 0.001) in 1Y. The incidence of sarcopenic obesity increased from 23.7% to 47.4% during 1Y of treatment. Baseline waist circumference was a positive predictor of increase in VAT (p = 0.037). No exposure-toxicity relationship was found. In-depth analysis showed increased appetite in two patients and metabolic syndrome in all four patients. Conclusions: Alectinib caused significant increased abdominal obesity, sarcopenic obesity, SAT and VAT quickly after initiation. This may lead to serious metabolic disturbances in long-surviving patients. Body composition analysis. n = 46* Relative difference Baseline body composition Waist circumference in cm (n = 44) VAT surface area in cm 2 VAT/SM index SAT surface area in cm 2 (n = 44) 94 ± 12 90 [50, 173] 0.7 [0.4, 1.3] 184 ± 82 Change during first year in cm 2 (%) † Waist circumference in cm (%) (n = 32) VAT (n = 38) VAT/SM index (n = 38) SAT (n = 32) +9.0 ± 6.1 +35.7 [16.2, 94.6] 1.1 [0.6, 2.1] +45.4 [17.2, 85.0] +9.7%, p < 0.001 +39.0%, p < 0.001 +48.7%, p < 0.001 +33.3%, p < 0.001 Numeric variables are reported as mean ± SD or median [IQR] depending on normality. The relative difference was calculated using the paired T-test, related-samples Wilcoxon signed rank test, or McNemar test. Abbreviations: n = number of patients, SAT = subcutaneous adipose tissue, SD = standard deviation, SM = skeletal muscle, VAT = visceral adipose tissue.* n = 46 unless mentioned otherwise; † Compared to baseline.