Braf-mutant metastatic non-small-cell lung cancer: Real world data from the Italian biomarker atlas database

  • Eur J Cancer. 2026 Feb 5:234:116191. doi: 10.1016/j.ejca.2025.116191.
Claudio Sini  1 ,  Alessandro Russo  2 ,  Diego Cortinovis  3 ,  Lucia Anna Muscarella  4 ,  Marcello Tiseo  5 ,  Emilio Bria  6 ,  Salvatore Grisanti  7 ,  Pierluigi Piovano  8 ,  Antonello Veccia  9 ,  Lorenzo Antonuzzo  10 ,  Fabrizio Citarella  11 ,  Sara Pilotto  12 ,  Maria Lucia Reale  13 ,  Daniele Pignataro  14 ,  Elisa Roca  15 ,  Lorenzo Calvetti  16 ,  Pamela Pizzutilo  17 ,  Gabriele Minuti  18 ,  Giacomo Pelizzari  19 ,  Greta Alì  20 ,  Anna Bettini  21 ,  Alberto Pavan  22 ,  Diego Signorelli  23 ,  Serena Ricciardi  24 ,  Giulia Meoni  25 ,  Concetta Sergi  26 ,  Carlo Genova  27 ,  Vieri Scotti  28 ,  Tiziana Vavalà  29 ,  Stefania Gori  30 ,  Giulia Pasello  31 ,  Paolo Pedrazzoli  32 ,  Rita Chiari  33 ,  Alessandro D'Aveni  34 ,  Roberta Buosi  35 ,  Luca Toschi  36 ,  Hector Soto Parra  37 ,  Lucio Buffoni  38 ,  Brigida Stanzione  39 ,  Cinzia Ortega  40 ,  Cristina Zannori  41 ,  Diana Giannarelli  42 ,  Umberto Malapelle  43 ,  Silvia Novello  44 ,  Francesco Passiglia  45 ,  Editta Baldini  46
Affiliations
  • 1. Medical Oncology, CPDO, Ospedale Giovanni Paolo II, Olbia, Italy.
  • 2. Medical Oncology Department, Humanitas Istituto Clinico Catanese, Misterbianco, Catania, Italy; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.
  • 3. Fondazione IRCCS San Gerardo dei Tintori Monza, Monza/ University of Milano-Bicocca, Italy.
  • 4. Laboratory of Oncology, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo 71013, Italy.
  • 5. Department of Medicine and Surgery, University of Parma and Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
  • 6. Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Ospedale Isola Tiberina - Gemelli Isola, Rome, Italy.
  • 7. Medical Oncology-ASST-Spedali Civili, Brescia, Italy.
  • 8. Medical Oncology-AO SS Antonio e Biagio, Alessandria, Italy.
  • 9. Medical Oncology, Ospedale di Trento, Italy.
  • 10. Medical Oncology, AOU Careggi-Firenze, Italy.
  • 11. Medical Oncology Department, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.
  • 12. Section of Innovation Biomedicine - Oncology Area, Department of Engineering for Innovation Medicine (DIMI), University of Verona and University and Hospital Trust (AOUI) of Verona, Italy.
  • 13. Medical Oncology Unit, Vito Fazzi Hospital, Lecce, Italy.
  • 14. Medical Oncology, Ospedale Cardinal Massaia, Asti, Italy.
  • 15. Thoracic Oncology - Lung Unit, P. Pederzoli Hospital, Peschiera Del Garda, VR, Italy.
  • 16. Medical Oncology, East district - AULSS 8 BERICA, Vicenza, Italy.
  • 17. Medical Thoracic Oncology Unit IRCCS Istituto Tumori Giovanni Paolo II Bari, Italy.
  • 18. Clinical Trial Unit: Phase 1 and Precision Medicine, National Cancer Institute, IRCCS, Regina Elena, Rome, Italy.
  • 19. Department of Oncology, Azienda sanitaria universitaria Friuli Centrale, Udine, Italy.
  • 20. Pathological Anatomy,Surgical, Medical, Molecular and Critical Care Pathology Department, University Hospital of Pisa, Pisa, Italy.
  • 21. Medical Oncology, ASST Papa Giovanni XXIII, Bergamo, Italy.
  • 22. Department of Medical Oncology, AULSS 3 Serenissima, Venezia, Italy.
  • 23. Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
  • 24. Medical Oncology, San Camillo Forlanini Hospital, Roma, Italy.
  • 25. SOS Medical Oncology, San Giovanni di Dio Hospital, Firenze, Italy.
  • 26. Oncology Unit ARNAS Garibaldi Nesima, Catania, Italy.
  • 27. Academic Medical Oncology Unit, IRCCS Ospedale Policlinico San Martino, Genoa 16132, Italy; Department of Internal Medicine and Medical Specialties, University of Genoa, Italy.
  • 28. Radiation Oncology Unit, Oncology Department, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
  • 29. AOU Città della Salute e della Scienza-Dipartimento di Oncologia, SC Oncologia 1U, Torino, Italy.
  • 30. IRCCS Sacro Cuore Don Calabria, Negrar di Valpolicella, Italy.
  • 31. Oncology 2, Istituto Oncologico Veneto IOV IRCCS, Padova, Italy; Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
  • 32. Medical Oncology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Internal Medicine, University of Pavia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
  • 33. Medical Oncology Unit, AST1, Pesaro 61121, Italy.
  • 34. Medical Oncology Unit, P.O. Saronno - ASST Valle Olona, Saronno, Italy.
  • 35. Department of Medical Oncology, Ospedale Santo Spirito, Casale Monferrato, Alessandria, Italy.
  • 36. Medical Oncology and Haematology Unit, IRCCS Humanitas Research Hospital, Milan, Italy.
  • 37. Medical Oncology, Azienda Ospedaliero Universitaria Policlinico "G. Rodolico-S. Marco", Catania, Italy.
  • 38. Medical Oncology, Humanitas Gradenigo Hospital, Torino, Italy.
  • 39. Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano 33081, Italia.
  • 40. Division of Oncology, Institute for Cancer Research and Treatment, Asl Cn2 -Alba-Brà, Italy.
  • 41. Medical and Translational Oncology,Department of Oncology, Azienda Ospedaliera Santa Maria, Terni, Italy.
  • 42. Fondazione Policlinico Universitario A. Gemelli, IRCCS - Facility of Epidemiology and Biostatistics, Rome, Italy.
  • 43. Department of Public Health, University Federico II of Naples, Naples, Italy.
  • 44. Department of Oncology, University of Turin, San Luigi Hospital, Orbassano, Turin, Italy. Electronic address: [email protected].
  • 45. Department of Oncology, University of Turin, San Luigi Hospital, Orbassano, Turin, Italy.
  • 46. Medical Oncology, Azienda Sanitaria Toscana, Lucca, Nord, Italy.
PMID: 41475048 DOI: 10.1016/j.ejca.2025.116191
Abstract

Background: BRAF mutations identify a small subgroup of patients (pts) with non-small cell lung Cancer (NSCLC). Dabrafenib/trametinib (D/T) combination is associated with high response rates and durable anti-tumor activity in BRAF-V600-mutants. Several open questions still remain unanswered in clinical practice, including the efficacy of treatments based on clinical and molecular characteristics, the activity in patients with brain metastases, the optimal sequence with immunotherapy-based therapies. Here we present outcomes among advanced BRAF-mutant NSCLC patients from the Italian ATLAS registry.

Methods: Patients with metastatic BRAF-mutated NSCLC were included. Clinical-pathological features, treatment effectiveness and safety outcomes were retrospectively collected from the Italian real-world ATLAS registry.

Results: A total of 244 BRAF-mutated NSCLC pts were enrolled, including 70 % V600E mutations. The median PFS of first line D/T was 19.8 months (95 % CI: 10.7-29.0), with a 2-year OS rate of 65.4 % and a PFS2 of 6.6 months (95 % CI: 0-14.3). The activity of D/T differs among sex (mPFS was 13.6 mos and 25.3 mos and 2-yr OS rate were 54.9 % and 72.3 % in males and females, respectively) and smoking status (mPFS was 18.4 mos, 25.6 mos and 24 mos in never, former and current smokers, respectively). Concomitant MET amplification was associated with a shorter median PFS (mPFS was 13.6 mos vs. 44.3 mos with and without MET amplification respectively) in pts treated with D/T as 1st line.

Conclusions: These data confirm the efficacy and safety of first line D/T in BRAF V600E-mutated pts in the real-world setting consistently with prior studies, suggesting a differential activity among key clinical-molecular subgroups.

Keywords
BRAF V600E; BRAF mutations; Dabrafenib; Immunotherapy; NSCLC; Real-world evidence; Trametinib.
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