Illini Oliver, Fabikan Hannah, Breitenecker Kristina, Lang-Stöberl Anna Sophie, Krainer Julie, Krenbek Dagmar, Weinlinger Christoph, Watzka Stefan, Valipour Arschang, Hochmair Maximilian J
Department of Respiratory and Critical Care Medicine, Clinic Floridsdorf, Vienna Healthcare Group, Vienna, Austria.
Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Clinic Floridsdorf, Vienna, Austria.
Medicine (Baltimore). 2025 Apr 25;104(17):e42297. doi: 10.1097/MD.0000000000042297.
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.
间变性淋巴瘤激酶（ALK）阳性非小细胞肺癌（NSCLC）尽管接受了酪氨酸激酶抑制剂（TKI）治疗，仍常出现不完全缓解和疾病进展。初步数据表明，将ALK选择性TKI布加替尼与手术或放疗联合使用可能会改善治疗效果。我们回顾性分析了接受布加替尼作为一线治疗并联合局部治疗的晚期ALK阳性NSCLC患者，以评估这种方法在实际临床环境中的安全性和有效性。9例患者中，6例（67%）为Ⅲ期，3例（33%）为Ⅳ期腺癌。5例患者接受了手术，3例接受了放疗，1例同时接受了手术和放疗。78%的患者发生了与布加替尼相关的不良事件（AE），主要为轻度（≤2级）。22%的患者出现了严重AE（≥3级），包括呼吸困难和高血压。22%的患者因毒性而停用布加替尼。与局部治疗相关的AE大多为1级。客观缓解率为89%，其中2例完全缓解，6例部分缓解。在数据截止时，55%的患者仍在接受布加替尼治疗，中位治疗持续时间为14个月，2年无进展生存率为100%。布加替尼与局部治疗联合应用似乎对晚期ALK阳性NSCLC安全且可能更有效。有必要进行进一步研究。
