Oliver Gautschi1, Julie Milia, Bastien Cabarrou, Marie-Virginia Bluthgen, Benjamin Besse, Egbert F Smit, Juergen Wolf, Solange Peters, Martin Früh, Dieter Koeberle, Youssouf Oulkhouir, Martin Schuler, Alessandra Curioni-Fontecedro, Benjamin Huret, Mallorie Kerjouan, Sebastian Michels, Georg Pall, Sacha Rothschild, Gerald Schmid-Bindert, Matthias Scheffler, Rémi Veillon, Luciano Wannesson, Joachim Diebold, Gérard Zalcman, Thomas Filleron, Julien Mazières. 1. *Tumorzentrum, Luzerner Kantonsspital, Luzern, Switzerland; †Hôpital Larrey, Centre Hospital-Universitaire, Université Paul Sabatier, Toulouse, France; ‡Institut Claudius Regaud IUCT-O, Toulouse, France; §Institut Gustave Roussy, Villejuif, France; ¶VU University Medical Center, Amsterdam, The Netherlands; ‖Center of Integrated Oncology Cologne, University Hospital Cologne, Cologne, Germany; #Centre Pluridisciplinaire d'Oncologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; **Onkologie/Hämatologie, Kantonsspital St. Gallen, St. Gallen, Switzerland; ††Medizinische Klinik, St. Claraspital, Basel, Switzerland; ‡‡Service de pneumologie et oncologie thoracique, Hopital Universitaire, Caen, France; §§University Hospital Essen, Essen, Germany; ¶¶University Hospital Zurich, Zurich, Switzerland; ‖‖Clinique Teissier, Valenciennes, France; ##Centre Hospitalier Intercommunal de Creteil, Créteil, France; ***University Hospital Innsbruck, Innsbruck, Austria; †††University Hospital Basel, Basel, Switzerland; ‡‡‡Heidelberg University Medical Center, Mannheim, Germany; §§§Hopital du Haut Lévèque, Pessac, France; ¶¶¶Oncology Institute of Southern Switzerland, Bellinzona, Switzerland; and ‖‖‖Centre Hospitalier Universitaire, Université de Caen-Basse Normandie, Caen, France.
Abstract
INTRODUCTION: Approximately 2% of lung adenocarcinomas have BRAF (v-Raf murine sarcoma viral oncogene homolog B) mutations, including V600E and other types. Vemurafenib, dabrafenib, and sorafenib as BRAF inhibitors are currently tested in clinical trials, but access for patients is limited. The aim of this study was to document the clinical course of patients treated outside of clinical trials. METHODS: We conducted a retrospective multicenter cohort study in Europe of patients with advanced BRAF-mutant lung cancer treated with known BRAF inhibitors. Data were anonymized and centrally assessed for age, gender, smoking, histology, stage, local molecular diagnostic results, systemic therapies, and survival. Best response was assessed locally by RECIST1.1. RESULTS: We documented 35 patients treated in 17 centers with vemurafenib, dabrafenib, or sorafenib. Median age was 63 years (range 42-85); gender was balanced; 14 (40%) were never smokers; all (100%) had adenocarcinoma; 29 (83%) had V600E; 6 (17%) had other mutations; one of them had a concomitant KRAS mutation. Thirty (86%) patients had chemotherapy in the first line. Overall survival with first-line therapy was 25.3 months for V600E and 11.8 months for non-V600E. Thirty-one patients received one BRAF inhibitor, and four received a second inhibitor. Overall response rate with BRAF therapy was 53%, and disease control rate was 85%. Median progression-free survival with BRAF therapy was 5.0 months, and overall survival was 10.8 months. CONCLUSIONS: These results confirm the activity of targeted therapy in patients with BRAF-mutant lung adenocarcinoma. Further trials are warranted to study combination therapies and drug resistance mechanisms.
INTRODUCTION: Approximately 2% of lung adenocarcinomas have BRAF (v-Raf murine sarcoma viral oncogene homolog B) mutations, including V600E and other types. Vemurafenib, dabrafenib, and sorafenib as BRAF inhibitors are currently tested in clinical trials, but access for patients is limited. The aim of this study was to document the clinical course of patients treated outside of clinical trials. METHODS: We conducted a retrospective multicenter cohort study in Europe of patients with advanced BRAF-mutant lung cancer treated with known BRAF inhibitors. Data were anonymized and centrally assessed for age, gender, smoking, histology, stage, local molecular diagnostic results, systemic therapies, and survival. Best response was assessed locally by RECIST1.1. RESULTS: We documented 35 patients treated in 17 centers with vemurafenib, dabrafenib, or sorafenib. Median age was 63 years (range 42-85); gender was balanced; 14 (40%) were never smokers; all (100%) had adenocarcinoma; 29 (83%) had V600E; 6 (17%) had other mutations; one of them had a concomitant KRAS mutation. Thirty (86%) patients had chemotherapy in the first line. Overall survival with first-line therapy was 25.3 months for V600E and 11.8 months for non-V600E. Thirty-one patients received one BRAF inhibitor, and four received a second inhibitor. Overall response rate with BRAF therapy was 53%, and disease control rate was 85%. Median progression-free survival with BRAF therapy was 5.0 months, and overall survival was 10.8 months. CONCLUSIONS: These results confirm the activity of targeted therapy in patients with BRAF-mutant lung adenocarcinoma. Further trials are warranted to study combination therapies and drug resistance mechanisms.
Authors: T Vosecka; A Vicha; T Zelinka; P Jencova; K Pacak; J Duskova; J Benes; A Guha; L Stanek; M Kohoutova; Z Musil Journal: Neoplasma Date: 2017 Impact factor: 2.575
Authors: Oliver Gautschi; Julie Milia; Thomas Filleron; Juergen Wolf; David P Carbone; Dwight Owen; Ross Camidge; Vignhesh Narayanan; Robert C Doebele; Benjamin Besse; Jordi Remon-Masip; Pasi A Janne; Mark M Awad; Nir Peled; Chul-Cho Byoung; Daniel D Karp; Michael Van Den Heuvel; Heather A Wakelee; Joel W Neal; Tony S K Mok; James C H Yang; Sai-Hong Ignatius Ou; Georg Pall; Patrizia Froesch; Gérard Zalcman; David R Gandara; Jonathan W Riess; Vamsidhar Velcheti; Kristin Zeidler; Joachim Diebold; Martin Früh; Sebastian Michels; Isabelle Monnet; Sanjay Popat; Rafael Rosell; Niki Karachaliou; Sacha I Rothschild; Jin-Yuan Shih; Arne Warth; Thomas Muley; Florian Cabillic; Julien Mazières; Alexander Drilon Journal: J Clin Oncol Date: 2017-03-13 Impact factor: 44.544
Authors: D Isla; M Majem; N Viñolas; A Artal; A Blasco; E Felip; P Garrido; J Remón; M Baquedano; J M Borrás; M Die Trill; R García-Campelo; O Juan; C León; P Lianes; F López-Ríos; L Molins; M Á Planchuelo; M Cobo; L Paz-Ares; J M Trigo; J de Castro Journal: Clin Transl Oncol Date: 2016-11-24 Impact factor: 3.405
Authors: Alessandro Russo; Ana Rita Lopes; Michael G McCusker; Sandra Gimenez Garrigues; Giuseppina R Ricciardi; Katherine E Arensmeyer; Katherine A Scilla; Ranee Mehra; Christian Rolfo Journal: Curr Oncol Rep Date: 2020-04-16 Impact factor: 5.075
Authors: Svetlana A Protsenko; Anna I Semionova; Yuri I Komarov; Svetlana N Aleksakhina; Alexandr O Ivantsov; Aglaya G Iyevleva; Evgeny N Imyanitov Journal: Invest New Drugs Date: 2015-08-20 Impact factor: 3.850