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

Leßmann ME, Saalfeld FC, Ruge L, Kauffmann-Guerrero D, Illini O, Stenzinger A, Minuth-Fuchs K, Rittmeyer A, Goetting I, Schildknecht K, Eul B, Schubart C, Rothschild SI, Grohé C, Armster K, Mohorčič K, Janzic U, Waller CF, Overbeck TR, Vesce R, Schulte H, Mauti LA, Stephan-Falkenau S, Wiesweg M, Faehling M, Gerstenmaier U, Schmid S, Kian W, Lozynskyy R, Ivanović M, Syrigos K, Simon R, Merkelbach-Bruse S, Wenzel C, Brückmann S, Herold S, Aust DE, Thomas M, Hochmair MJ, Tufman A, Rasokat A, Christopoulos P, Wermke M (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Book Volume: 10

Article Number: 248

Journal Issue: 1

DOI: 10.1038/s41698-026-01486-y

Abstract

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.

Involved external institutions

Klinik Floridsdorf Austria (AT) Lungenfachklinik Immenhausen Germany (DE) Kantonsspital Baden Switzerland (CH) Evangelische Lungenklinik Berlin gGmbH Germany (DE) Karl Landsteiner Privatuniversität für Gesundheitswissenschaften GmbH Austria (AT) University Clinic Golnik / Klinika Golnik Slovenia (SI) Universitätsklinikum Carl Gustav Carus Dresden Germany (DE) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Maribor University Medical Centre (Maribor UMC) / Univerzitetni klinični center Maribor Slovenia (SI) Kantonsspital Winterthur (KSW) Switzerland (CH) Städtische Kliniken Esslingen Germany (DE) Inselspital, Universitätsspital Bern Switzerland (CH) Samson Assuta Ashdod University Hospital / Assuta Ashdod Medical Center Israel (IL) National and Kapodistrian University of Athens Greece (GR)

How to cite

APA:

Leßmann, M.E., Saalfeld, F.C., Ruge, L., Kauffmann-Guerrero, D., Illini, O., Stenzinger, A.,... Wermke, M. (2026). Beyond EML4: efficacy of targeted therapy in lung cancer patients with rare ALK fusions – a real-world retrospective analysis. npj Precision Oncology, 10(1). https://doi.org/10.1038/s41698-026-01486-y

MLA:

Leßmann, Marie Elisabeth, et al. "Beyond EML4: efficacy of targeted therapy in lung cancer patients with rare ALK fusions – a real-world retrospective analysis." npj Precision Oncology 10.1 (2026).

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