P84.11 Real-World Brigatinib Dosing Patterns in Patients with Anaplastic Lymphoma Kinase Positive Non-Small Cell Lung Cancer in the United States

Abstract

Standard dosing of brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor for treating ALK+ non-small cell lung cancer is 90 mg once daily for 7 days then escalated to 180 mg on Day 8 as tolerated. Among patients receiving this standard dose, 29% in the post-crizotinib ALTA trial and 38% in the tyrosine kinase inhibitor (TKI)-naïve ALTA-1L trial required a dose reduction. Asymptomatic laboratory abnormalities including creatine phosphokinase, amylase or lipase elevations were common causes of dose reductions in these studies. Outside of trial protocol mandated dosing, real-world dosing patterns of brigatinib have not been previously described. Adult (≥18 years) patients with ≥1 claim for brigatinib were identified between 01 April 2017 and 31 August 2019 from the IQVIA longitudinal 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 the day supply. Dose reduction was defined as ≥30 days of supply with ADD < 180 mg/day after reaching 180 mg/day, or < maximum (max) dose in patients who did not reach 180 mg/day. Time to dose reduction from 180 mg/day or max dose and probability of continued therapy at ≥180 mg/day or max dose were assessed via Kaplan-Meier analysis. Adherence was defined using medication possession ratio (MPR) and dose compliance score (DCS) was calculated as total dosage received divided by total dosage expected. A total of 240 brigatinib patients were identified. Median age was 58 years, 57.9% were female and 85.4% had ≥1 prior TKI. Mean (standard deviation) follow-up time was 10.7 (7.6) months. A dose of 180 mg/day was achieved in 202 (84.2%) patients, of which 87.1% were treated after 1+ prior lines. Dose reduction occurred in 15.8% of patients who reached 180 mg/day, and the probability of continued therapy at ≥180 mg/day in patients still on therapy at 3 and 6 months after dose escalation was 89.5% and 86.0%, respectively. Of the patients with dose reduction, 43.8% reduced to 120 mg/day. A total of 38 (15.8%) patients did not reach 180 mg/day. Dose reduction occurred in 13.2% of these patients, and the probability of continued therapy at the max dose at 3 and 6 months after max dose was reached was 94.1% and 89.8%, respectively. Among the patients with dose reduction, 40.0% reduced to 90 mg/day. Adherence and dose compliance were high overall with 93.3% of patients having MPR > 80% and median DCS of 1.0 (0.3-2.2). Real-world data suggest that standard dose escalation (90 to 180 mg) occurs in most brigatinib patients (>84%) and that dose reduction rates may be lower outside the protocol mandated confines of clinical trials. Adherence and dose compliance were high. Analysis with longer follow-up time may be warranted to further evaluate these findings.