Simple SummaryALK-rearranged non-small cell lung cancer treatment has radically changed in the last few years thanks to the development of ALK inhibitors, which clearly improved survival. To our knowledge, even though many studies correlate body mass index (BMI) with lung cancer immunotherapy, conflicting results have emerged in non-smoker patients treated with other drugs. Indeed, it is unclear whether body size variables and metabolism could affect ALK-inhibitor efficacy. The aim of this retrospective study is to correlate BMI status with survival outcomes in patients treated with commonly used ALK inhibitors in different lines of treatment. We observed that BMI status could impact survival outcomes, particularly in patients treated with Alectinib as the first line. Further prospective studies should examine this interesting phenomenon.AbstractNo evidence exists as to whether body mass index (BMI) impairs clinical outcomes from ALK inhibitors (ALKi) in patients with ALK-rearranged non-small cell lung cancer (NSCLC). Retrospective data of patients affected by metastatic ALK-rearranged NSCLC treated with ALKi were collected. We divided patients into “low- BMI” (≤25 kg/m2) and “high- BMI” (>25 kg/m2) categories and correlated them with overall survival (OS) and progression-free survival (PFS). We included 40 patients treated with ALKi. We observed a 3-year OS of 81.5% in high-BMI vs. 49.6% in low-BMI categories (p= 0.049); the 3-year first-line PFS was superior in high-BMI vs. low-BMI patients (47% vs. 19%,p= 0.019). As expected, patients treated with Alectinib had a 55.6% 3-year PFS vs. 7.1% for others treated with ALKi (p= 0.025). High-BMI was associated with a 100% 3-year PFS rate vs. 25.4% in low-BMI Alectinib patients (p= 0.03). BMI was independently correlated with first-line PFS and OS at multivariate analysis with PS (HR 0.39, CI 95% 0.16–0.96,p= 0.042; HR 0.18, CI 95% 0.05–0.61,p= 0.006). High-BMI was associated with higher efficacy in ALK-rearranged patients. These results are particularly exciting for Alectinib and could be correlated to mechanisms that should be investigated in subsequent prospective studies.