Real-world tolerability of front-line brigatinib in patients with anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC) with and without brain metastases in the United States.
Authors: Tai Edmund W. , Lin Huamao Mark , Wu Yanyu , Wan Yin , Gorritz Magdaliz , Zhou Xiaoyu , Chen Chi-Chang , Chen Yuanbin 
Published: October 2023

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Background: Brigatinib, a next-generation ALK tyrosine kinase inhibitor (TKI), is approved for treatment in patients with ALK+ NSCLC with a dosing schedule of 180 mg/day after a 7-day lead-in at 90 mg/day. Brigatinib has been shown through clinical trials to have improved intracranial efficacy compared to crizotinib. There is limited information regarding the real-world tolerability of brigatinib in patients with brain metastases (BM). Our study aims to assess treatment tolerability via dose reduction rates and adherence in patients treated with front-line (FL) brigatinib and stratified by evidence of BM. Methods: This retrospective cohort study utilized the IQVIA open-source pharmacy and medical claims databases. Adults (≥18 years) with ≥1 claim for brigatinib between 22 May 2020 and 31 December 2022 with no prior claims for brigatinib or other ALK-TKI therapies were identified from the pharmacy claims database and followed until the earliest of dose reduction, treatment discontinuation, or end of follow-up. Average daily dose (ADD) was calculated as the product of pill strength and quantity of pills dispensed divided by day supply. Dose reduction was defined as ≥30 days of treatment with ADD < 180 mg/day. Time to dose reduction from 180 mg/day and probability of continued therapy at ≥180 mg/day were assessed by Kaplan-Meier analysis. Adherence was defined using medication possession ratio (MPR) and calculated as the total day supply divided by the number of days from the first claim date to the last supply date of FL brigatinib. BM was defined as having ≥1 claim in the medical claims database with a diagnosis code for secondary malignant neoplasm of the brain. Results: Overall 126 patients treated with FL brigatinib were identified (median age: 57.5; 57.1% female). Median (min-max) follow-up time was 11.7 (1.0-30.7) months; 114 (90.5%) patients reached a dose of 180 mg/day, and among these 27 (23.7%) had evidence of BM. Of patients who reached a dose of 180 mg/day, 14.8% of those with BM and 18.4% with no BM (p=0.779) had a dose reduction. The probability of remaining on therapy at 180 mg/day was 86.2% at 3, 6 and 9 months and 71.8% at 12 months in patients with BM. In patients with no BM, the probabilities of remaining on therapy at a dose of 180 mg/day at 3, 6, 9 and 12 months were 89.1%, 82.6%, 70.8% and 67.1%, respectively (P=.761). Adherence was high irrespective of BM with 81.5% of patients with BM and 94.3% those without BM having MPR > 80%. Results in the overall FL brigatinib sample (with and without BM) were similar. Conclusions: Real-world data suggest that FL brigatinib is well tolerated regardless of brain metastasis status. Most FL brigatinib patients in the study achieved and maintained a daily dose of 180 mg. Dose reductions and probability of remaining on therapy were similar for patients with or without brain metastases.