Efficacy and Safety of Continuing Next-Generation ALK TKIs With Chemotherapy for Advanced ALK-Positive NSCLC: A Multicenter Retrospective Study

作者：Sarah Waliany, Shambo Guha Roy, Federica Pecci, Urs Weber, Fangdi Sun, Zhaohui Arter, Meghanne Lomibao, Joao V. Alessi, Mizuki Nishino, Faustine Luo, Matteo Repetto, Christina J. Falcon, Andrew Do, Jennifer Peterson, Joyce Liang, Audrey Liu, Misako Nagasaka, Biagio Ricciuti, Alexander Drilon, Sai‐Hong Ignatius Ou, Joel W. Neal, Tejas Patil, Mark M. Awad, Beow Y. Yeap, Subba R. Digumarthy, Jessica J. Lin · 发表于：Journal of the National Comprehensive Cancer Network · 年份：2025 · DOI：10.6004/jnccn.2025.7071 · 被引用次数：1 · 研究领域：Lung Cancer Treatments and Mutations、Lung Cancer Diagnosis and Treatment、Melanoma and MAPK Pathways

BACKGROUND: Next-generation ALK tyrosine kinase inhibitors (TKIs; eg, alectinib, brigatinib, ceritinib, ensartinib, lorlatinib) are established first-line therapies for patients with ALK fusion-positive (ALK+) advanced/metastatic non-small cell lung cancer (NSCLC). Chemotherapy-with platinum/pemetrexed (PT/Pem) as the preferred regimen-is considered standard next-line therapy. However, limited data exist on outcomes of continuing next-generation ALK TKIs with subsequent PT/Pem after progression on TKI monotherapy. PATIENTS AND METHODS: This multicentered, retrospective study included patients with ALK+ metastatic NSCLC who received PT/Pem alone or with alectinib or lorlatinib (PT/Pem/TKI) after progression on next-generation ALK TKIs. Endpoints included progression-free survival (PFS), overall survival (OS), 12-month cumulative incidence of intracranial progression, and treatment-related adverse events (trAEs). RESULTS: We identified 156 patients, of whom 86 received PT/Pem and 70 received PT/Pem/TKI (alectinib: n=23; lorlatinib: n=47). Median PFS was numerically longer with PT/Pem/TKI versus PT/Pem (6.0 vs 3.5 months; hazard ratio [HR], 0.75; P=.11). In 78 patients treated with the current paradigm of first-line next-generation ALK TKIs, PT/Pem/TKI was associated with longer median PFS (6.6 vs 3.5 months; HR, 0.58; P=.042) and longer median OS (16.4 vs 11.4 months; HR, 0.55; P=.041) than PT/Pem alone. Among patients evaluable for intracranial outcomes (n=98), treatment with ...