Beyond EML4: efficacy of targeted therapy in lung cancer patients with rare ALK fusions – a real-world retrospective analysis

作者：Marie-Elisabeth Leßmann, Felix Carl Saalfeld, Lea Ruge, Diego Kauffmann-Guerrero, Oliver Illini, Albrecht Stenzinger, Kaija Minuth-Fuchs, Achim Rittmeyer, Isabell Goetting, Katharina Schildknecht, Bastian Eul, Christoph Schubart, Sacha I. Rothschild, Christian Grohé, Karin Armster, Katja Mohorčič, Urška Janžič, Cornelius F. Waller, Tobias Raphael Overbeck, Rita Vesce, Hanna Schulte, Laetitia Mauti, Susann Stephan-Falkenau, Marcel Wiesweg, Martin Faehling, Uwe Gerstenmaier, Sabine Schmid, Waleed Kian, R. Lozynskyy, Marija Ivanović, Konstantinos Syrigos, Ronald Simon, Sabine Merkelbach‐Bruse, Carina Wenzel, Sascha Brückmann, Sylvia Herold, Daniela E. Aust, Michael Thomas, Maximilian J. Hochmair, Amanda Tufman, Anna Rasokat, National Network Genomic Medicine Lung Cancer (nNGM), Petros Christopoulos, Martin Wermke · 发表于：npj Precision Oncology · 年份：2026 · DOI：10.1038/s41698-026-01486-y · 研究领域：Lung Cancer Treatments and Mutations、Lung Cancer Diagnosis and Treatment、Lung Cancer Research Studies

Evidence on prognosis and optimal treatment for patients with advanced NSCLC harboring non-EML4-ALK fusions (rare ALK) remains limited. In a retrospective real-world cohort from 29 centers across six countries, overall survival (OS) appeared shorter in patients with rare ALK fusions (n = 51) compared with those with EML4-ALK fusions (n = 277; median 27 vs. 57 months, p = 0.08). Among patients receiving first-line therapy, those with rare ALK fusions experienced significantly shorter progression-free survival (PFS) with platinum-based chemotherapy than with a TKI (5 vs. 23 months; HR 3.1, 95% CI 1.2-8, p = 0.02). In contrast, for patients treated first-line with an ALK-TKI, ORR (85% vs. 74%; p = 0.9) and PFS (median 25 vs. 23 months; HR 0.9, 95% CI 0.6-1.5) were similar between rare ALK and EML4-ALK groups. These findings support TKIs as preferred first-line therapy for advanced NSCLC with rare ALK fusions.