98O_PR - Targeted therapy for BRAF-mutant lung cancer: Results from the European EURAF cohort study

Date 17 April 2015
Event ELCC 2015
Session Advanced NSCLC
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Presenter Oliver Gautschi
Citation Annals of Oncology (2015) 0 (0): 1-8. 10.1093/annonc/mdv128
Authors O. Gautschi1, M.V. Bluthgen2, E.F. Smit3, J. Wolf4, M. Früh5, S. Peters6, M. Schuler7, G. Zalcman8, J. Milia9, J. Mazieres9
  • 1Medical Oncology, Luzerner Kantonsspital, 6004 - Luzern/CH
  • 2Iot Institut D'oncologie Thoracique, Gustave Roussy, Paris/FR
  • 3Dept. Of Pulmonary Diseases, Vrije University Medical Centre (VUMC), 1081 HV - Amsterdam/NL
  • 4Cio Center For Integrated Oncology, University of Cologne, Köln/DE
  • 5Hematology/oncology, Kantonsspital St. Gallen, St. Gallen/CH
  • 6Oncology, Centre Hospitalier Universitaire Vaudois - CHUV, 1011 - Lausanne/CH
  • 7Innere Klinik (tumorforschung), Westdeutsches Tumorzentrum Essen, Essen/DE
  • 8Service De Pneumologie, CHU de Caen, 14033 - Caen/FR
  • 9Thoracic Oncology, CHU Toulouse, Hôpital de Larrey, 31059 - Toulouse/FR

Abstract

Aim/Background

About 2% of lung adenocarcinomas have BRAF mutations. The BRAF inhibitors (BRAFi) vemurafenib (V) and dabrafenib (D) had promising activity in first clinical trials, but only few centers participated, and many patients (pts) were not enrolled. Our aim was to study the clinical course of those pts.

Methods

We conducted a retrospective ulticentre cohort study in Europe of pts with advanced BRAF-mutant lung cancer treated outside of a clinical trial. Data were anonymized and centrally assessed for age, gender, smoking, histology, stage, local molecular diagnostic results, systemic therapies, and survival. Best response was locally assessed by RECIST1.1. This academic study was conducted without industry support.

Results

By December 2014, 35 pts received individual BRAFi therapy in 17 participating centers. Median age at diagnosis was 64 years (range 43-85), 18 (51%) male, 16 (46%) current or former smoker. All 35 (100%) pts had lung adenocarcinoma histology, 29 (83%) had BRAF V600E, 6 (17%) had other BRAF mutations, 1 (3%) also had a concomitant KRAS mutation. 30 (86%) pts had prior chemotherapy, 5 (14%) had frontline BRAFi therapy. BRAFi used were V (28 pts), D (10 pts), and sorafenib (S, 1 pt). 31 (89%) pts received 1 BRAFi (24 V, 7 D) and 4 pts received 2 (V followed by D in 3 pts, S followed by V in 1 pt). Best response by RECIST was available for 36 (92%) of 39 BRAFi therapies: 2 (6%) CR, 17 (47%) PR, 13 (36%) SD, and 4 (11%) PD; overall response rate (ORR) was 53% (95%CI: 35-70%). Among the 6 pts with non-V600E, 1 (17%) achieved a PR. No unexpected toxicities were reported. Further results including updated survival will be presented at the meeting.

Conclusions

These results support BRAF testing in advanced lung adenocarcinoma, and BRAFi therapy in patients with V600E. Further studies are warranted to evaluate combination therapies and potential drug resistance mechanisms.

Disclosure

M. Schuler: Advisory role with compensation from Novartis and GSK.

All other authors have declared no conflicts of interest.