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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • National Network Genomic Medicine Lung Cancer (nNGM) - (Author)
  • Department of Internal Medicine I
  • Institute of Pathology
  • National Center for Tumor Diseases Dresden
  • University Hospital Carl Gustav Carus Dresden
  • National Network Genomic Medicine Lung Cancer (nNGM)
  • University of Cologne
  • Ludwig Maximilian University of Munich
  • Klinik Floridsdorf
  • Karl Landsteiner Society
  • Heidelberg University 
  • Translational Lung Research Center Heidelberg (TLRC) - DZL Heidelberg
  • University of Regensburg
  • Immenhausen Lung Clinic
  • University Hospital Tübingen
  • Robert Bosch Krankenhaus Stuttgart
  • Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie
  • University of Tübingen
  • Justus Liebig University Giessen
  • Friedrich-Alexander University Erlangen-Nürnberg
  • Cantonal Hospital Baden
  • Evangelical Lung Clinic Berlin
  • Karl Landsteiner University of Health Sciences
  • University Hospital Krems
  • University of Ljubljana
  • University Medical Center Freiburg
  • University of Göttingen
  • Heinrich Heine University Düsseldorf
  • University Hospital Frankfurt
  • Cantonal Hospital Winterthur
  • Fresenius AG
  • University Hospital Essen
  • Klinikum Esslingen
  • Ulm University
  • University of Bern
  • Samson Assuta Ashdod Medical Center
  • Shaare Zedek Medical Center
  • German Cancer Research Center (DKFZ)
  • General Hospital Maribor
  • National and Kapodistrian University of Athens
  • University of Hamburg

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.

Details

Original languageEnglish
Article number248
Journalnpj Precision Oncology
Volume10
Issue number1
Publication statusPublished - 29 Jun 2026
Peer-reviewedYes

External IDs

PubMedCentral PMC13314944
Scopus 105043473231

Keywords