Comparison of Efficacy and Safety of Brigatinib in First-Line Treatments for Patients with Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer: A Systematic Review and Indirect Treatment Comparison

(1) Background: The relative efficacy and safety of brigatinib compared with other next-generation anaplastic lymphoma kinase (ALK) inhibitors remains unclear, as first-line head-to-head trials have not been conducted. (2) Methods: Electronic databases were systematically searched for eligible randomized controlled trials (RCT) from January 2010 to October 2021. Outcomes evaluated by indirect treatment comparison (ITC) included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety. (3) Results: Nine RCTs with 2484 patients assessing crizotinib, ceritinib, alectinib, brigatinib, ensartinib, and lorlatinib were included. In intent-to-treat (ITT) patients, brigatinib significantly prolonged blinded independent review committee-assessed PFS compared with crizotinib (HR: 0.48, 95% CI: 0.35 to 0.66) and ceritinib (HR: 0.38, 95% CI: 0.23, 0.60) and had a comparable PFS with other 2nd-generation ALK inhibitors. Subgroup analyses of patients with baseline brain metastases and Asian patients yielded results similar to the base case. Brigatinib significantly reduced the risk of death compared with crizotinib (HR: 0.50, 95% CI: 0.28, 0.87) after adjusting for treatment crossover in the crizotinib arm. No significant differences were observed in OS between brigatinib and other next-generation ALK inhibitors. Brigatinib had significantly superior effects in ORR and intracranial ORR compared to crizotinib. The incidence of grade ≥3 AEs was similar between brigatinib and other next-generation ALK inhibitors (except for alectinib), while brigatinib could significantly delay the time to worsening in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) global health status (GHS)/quality of life (QoL) vs. crizotinib (HR: 0.69, 95% CI: 0.49, 0.98). (4) Conclusions: Brigatinib had longer PFS compared to crizotinib and ceritinib and had comparable efficacy and safety profile with other 2nd-generation ALK inhibitors in first-line treatments for patients with ALK-positive non-small-cell lung cancer