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Lancet Oncology, The

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Dabrafenib in patients with BRAFV600E-positive advanced non-small-cell lung cancer: a single-arm, multicentre, open-label, phase 2 trial - 04/05/16

Doi : 10.1016/S1470-2045(16)00077-2 
David Planchard, MD a, Tae Min Kim, MD b, Julien Mazieres, ProfMD c, d, Elisabeth Quoix, ProfMD e, Gregory Riely, MD f, g, Fabrice Barlesi, ProfMD h, Pierre-Jean Souquet, MD i, Egbert F Smit, ProfMD j, Harry J M Groen, ProfMD k, l, Ronan J Kelly, MD m, B C Cho, MD n, Mark A Socinski, ProfMD o, Lini Pandite, MD p, Christine Nase, BSN q, Bo Ma, PhD r, Anthony D’Amelio, PhD s, Bijoyesh Mookerjee, MD t, C Martin Curtis, BS u, Bruce E Johnson, ProfMD v, ⁎
a Department of Medical Oncology, Gustave Roussy, Villejuif, France 
b Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea 
c Thoracic Oncology Unit, Rangueil-Larrey Hospital, Toulouse, France 
d Paul Sabatier University, Toulouse, France 
e Pneumology Department, University Hospital of Strasbourg, Strasbourg, France 
f Department of Medicine, Thoracic Oncology Service, Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA 
g Joan and Sanfor I Weill Department of Medicine, Weill Cornell Medical College, New York, NY, USA 
h Multidisciplinary Oncology and Therapeutic Innovations Department, Aix-Marseille University, Assistance Publique Hôpitaux de Marseille, Livon, Marseille, France 
i Acute Respiratory Medicine and Thoracic Oncology Department, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France 
j Department of Pulmonary Diseases, Vrije Universiteit VU Medical Centre, Amsterdam, Netherlands 
k Department of Pulmonary Diseases, University of Groningen, Groningen, Netherlands 
l University Medical Center Groningen, Groningen, Netherlands 
m Upper Aerodigestive Malignancies Division, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA 
n College of Medicine, Yonsei University, Seoul, South Korea 
o Lung Cancer Section, Division of Hematology/Oncology, University of Pittsburgh, Pittsburgh, PA, USA 
p Adaptimmune LLC, Philadelphia, PA, USA 
q GlaxoSmithKline, Collegeville, Pennsylvania, PA, USA 
r Biothera, Eagan, MN, USA 
s Novartis Pharmaceuticals, King of Prussia, PA, USA 
t Novartis Pharmaceuticals, East Hanover, NJ, USA 
u Novartis Pharmaceuticals, Morrisville, NC, USA 
v Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA 

*Correspondence to: Prof Bruce E Johnson, Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USACorrespondence to: Prof Bruce E JohnsonDepartment of Medical OncologyDana-Farber Cancer Institute44 Binney StreetBostonMA02115USA

Summary

Background

Activating BRAFV600E (Val600Glu) mutations are found in about 1–2% of lung adenocarcinomas, which might provide an opportunity for targeted treatment in these patients. Dabrafenib is an oral selective inhibitor of BRAF kinase. We did a trial to assess the clinical activity of dabrafenib in patients with advanced non-small-cell lung cancer (NSCLC) positive for the BRAFV600E mutation.

Methods

In this phase 2, multicentre, non-randomised, open-label study, we enrolled previously treated and untreated patients with stage IV metastatic BRAFV600E-positive NSCLC. Patients received oral dabrafenib 150 mg twice daily. The primary endpoint was investigator-assessed overall response, which was assessed in patients who had received at least one dose of dabrafenib; safety was also assessed in this population. The study is ongoing but not enrolling patients in this cohort. This trial is registered with ClinicalTrials.gov, number NCT01336634.

Findings

Between Aug 3, 2011, and Feb 25, 2014, 84 patients were enrolled, six of whom had not previously received systemic treatment for NSCLC. 26 of the 78 previously treated patients achieved an investigator-assessed overall response (33% [95% CI 23–45]). Four of the six previously untreated patients had an objective response. One patient died from an intracranial haemorrhage that was judged by the investigator to be due to the study drug. Serious adverse events were reported in 35 (42%) of 84 patients. The most frequent grade 3 or worse adverse events were cutaneous squamous-cell carcinoma in ten (12%), asthenia in four (5%), and basal-cell carcinoma in four (5%).

Interpretation

Dabrafenib showed clinical activity in BRAFV600E-positive NSCLC. Our findings suggest that dabrafenib could represent a treatment option for a population of patients with limited therapeutic options.

Funding

GlaxoSmithKline.

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© 2016  Elsevier Ltd. Tous droits réservés.
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Vol 17 - N° 5

P. 642-650 - mai 2016 Retour au numéro
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