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

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月29日

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  • 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,
  • Urska Janzic,
  • Cornelius F. Waller,
  • Tobias Raphael Overbeck,
  • Rita Vesce,
  • Hanna Schulte,
  • Laetitia Arja Mauti,
  • Susann Stephan-Falkenau,
  • Marcel Wiesweg,
  • Martin Faehling,
  • Uwe Gerstenmaier,
  • Sabine Schmid,
  • Waleed Kian,
  • Rostyslav Lozynskyy,
  • Marija Ivanović,
  • Konstantinos Syrigos,
  • Ronald Simon,
  • Sabine Merkelbach-Bruse,
  • Carina Wenzel,
  • Sascha Brückmann,
  • Sylvia Herold,
  • Daniela E. Aust,
  • Michael Thomas,
  • Maximilian Johannes Hochmair,
  • Amanda Tufman,
  • Anna Rasokat,
  • Petros Christopoulos,
  • Martin Wermke

摘要

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.