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

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.

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Journal
npj Precision Oncology
Published
2026-06-29
DOI
https://doi.org/10.1038/s41698-026-01486-y
Primary Topic
Lung Cancer Treatments and Mutations
Type
article
Field-Weighted Citation Impact
0.00

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article

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

Susann Stephan-Falkenau, Marie-Elisabeth Leßmann, Uwe Gerstenmaier, Maximilian J. Hochmair et al.
npj Precision Oncology
Lung Cancer Treatments and Mutations
article

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

Susann Stephan-Falkenau, Marie-Elisabeth Leßmann, Uwe Gerstenmaier, Maximilian J. Hochmair, Petros Christopoulos, Sascha Brückmann, Martin Faehling, Christoph Schubart, Rita Vesce, Albrecht Stenzinger, Martin Wermke, Katja Mohorčič, Hanna Schulte, Achim Rittmeyer, Urška Janžič, Lea Ruge, Waleed Kian, R. Lozynskyy, Felix Carl Saalfeld, Oliver Illini, Isabell Goetting, Sabine Merkelbach‐Bruse, Laetitia Mauti, Anna Rasokat, Karin Armster, Michael Thomas, Konstantinos Syrigos, Sylvia Herold, Kaija Minuth-Fuchs, Katharina Schildknecht, Daniela E. Aust, Cornelius F. Waller, Christian Grohé, Tobias Raphael Overbeck, Carina Wenzel, Marija Ivanović, Ronald Simon, Diego Kauffmann-Guerrero, National Network Genomic Medicine Lung Cancer (nNGM), Sacha I. Rothschild, Bastian Eul, Marcel Wiesweg, Amanda Tufman, Sabine Schmid
article en

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.

npj Precision OncologyVol. 10(1)
Goethe University Frankfurt (DE), University of Ljubljana (SI), Universität Hamburg (DE), University of Freiburg (DE), German Cancer Research Center (DE), Friedrich-Alexander-Universität Erlangen-Nürnberg (DE), Universität Ulm (DE), Justus-Liebig-Universität Gießen (DE), Heidelberg University (DE), Assuta Medical Center (IL), University Hospital of Bern (CH), University Medical Center Freiburg (DE), Helmholtz-Zentrum Dresden-Rossendorf (DE), Shaare Zedek Medical Center (IL), University Hospital Heidelberg (DE), University Hospital of Basel (CH), Robert Bosch Hospital (DE), University Hospital Regensburg (DE), Ford (Germany) (DE), Universitätsklinikum Erlangen (DE), Düsseldorf University Hospital (DE), Helios Klinikum Emil von Behring (DE), Kantonsspital Winterthur (CH), University Medical Center Hamburg-Eppendorf (DE), National Institute of Genomic Medicine (MX), University Clinic of Pulmonary and Allergic Diseases Golnik (SI), Universitätsmedizin Göttingen (DE), Klinikum Esslingen (DE), Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology (DE), Universitätsklinikum Krems (AT), University Children's Hospital Tübingen (DE), German Center for Lung Research (DE), University Clinical Centre Maribor (SI), Universities of Giessen and Marburg Lung Center (DE), University Hospital Frankfurt (DE), Karl Landsteiner University of Health Sciences (AT), Evangelische Lungenklinik Berlin (DE), University Hospital Cologne (DE), University Medical Centre Mannheim (DE), Karl Landsteiner Society (AT), University Hospital Carl Gustav Carus (DE), Sotiria General Hospital (GR), Nationales Centrum für Tumorerkrankungen Dresden (DE), Heinrich Heine University Düsseldorf (DE), University of Duisburg-Essen (DE), Technische Universität Dresden (DE), University of Tübingen (DE), Ludwig-Maximilians-Universität München (DE)
Universität Basel, Deutsches Krebsforschungszentrum, Universitätsmedizin Göttingen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Albert-Ludwigs-Universität Freiburg, Technische Universität Dresden, Universitätsklinikum Regensburg, Ludwig-Maximilians-Universität München, Deutsche Krebshilfe, Ruhr-Universität Bochum, Univerza v Ljubljani, Universität zu Köln, Deutsches Zentrum für Lungenforschung, Universitätsklinikum Köln, Helmholtz-Zentrum Dresden-Rossendorf, Universitätsklinikum Erlangen, Universitätsklinikum Heidelberg, Karl Landsteiner Privatuniversität für Gesundheitswissenschaften
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