Abstract
Anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) often shows incomplete responses and progression despite tyrosine kinase inhibitor (TKI) therapy. Preliminary data suggest that combining brigatinib, an ALK-selective TKI, with surgery or radiotherapy may improve outcomes. We retrospectively analyzed patients with advanced ALK-positive NSCLC who received brigatinib as first-line treatment combined with local therapy to assess safety and efficacy of this approach in a real-world setting. Among 9 patients, 6 (67%) had stage III and 3 (33%) had stage IV adenocarcinoma. Five patients received surgery, 3 received radiotherapy, and 1 received both. Brigatinib-related adverse events (AEs) occurred in 78% of patients, primarily mild (grade ≤ 2). Severe AEs (grade ≥ 3) were seen in 22% of patients and included dyspnea and hypertension. Brigatinib was discontinued in 22% of patients due to toxicity. Local therapy-related AEs were mostly grade 1. The objective response rate was 89%, with 2 complete and 6 partial responses. At data cutoff, brigatinib was ongoing in 55% of patients, with a median treatment duration of 14 months and a 2-year progression-free survival rate of 100%. Combining brigatinib with local therapy appears safe and potentially more effective for advanced ALK-positive NSCLC. Further studies are warranted.