Vemurafenib in the French temporary authorization for use metastatic melanoma cohort: a single-centre trial.
Vemurafenib, a selective BRAF inhibitor, has recently shown an improved overall survival (OS) in metastatic melanoma with V600E mutation in phase 2 and 3 trials. Patients with BRAF V600E metastatic melanoma received vemurafenib orally, in the French temporary authorization for use program from April 2011 to April 2012. We analysed the clinical benefit and safety of vemurafenib. Secondary analyses included the impact of brain metastases on median OS and progression-free survival (PFS). Fifty patients were enrolled, of whom 20% had stage IIIC and 80% stage IV disease. The majority were men (58%), with a median age of 58 years (51-69). Forty-three patients had an Eastern Cooperative Oncology Group performance status of 0 or 1 (86%). Twenty patients had brain metastases (40%). Overall response rate was 53%. Complete response was achieved in five patients (10%), partial response in 21 patients (43%) and stable disease in seven patients (14%). Median OS was 7.5 months (95% confidence interval 5.6-12.7) and PFS was 3.6 months (95% confidence interval 2.9-5.9). Patients with brain metastasis had a response rate of 50% (nine partial response, one complete response), and median OS and PFS were, respectively, 4.3 and 3.1 months. Common adverse events were fatigue, arthralgia and cutaneous side effects. Sixteen per cent developed squamous cell carcinoma. Grade 3/4 was observed in 11 patients (22%). Six per cent required temporary discontinuation and/or dose reduction because of toxic effects. This study confirms the considerable clinical benefit of vemurafenib for patients with brain metastasis, with manageable toxicity.
Departments of aDermatology bPharmacy cPathology dPharmacology Laboratory, Saint Louis Hospital eDepartment of Biostatistics, Hotel Dieu Hospital fINSERM U976 gParis 7 Diderot University, Paris, France.
Feriel
F
Fennira
Cecile
C
Pagès
Pierre
P
Schneider
Irina
I
Sidina
Manuelle
M
Viguier
Nicole
N
Basset-Seguin
Nika
N
Madjlessi-Ezra
Isabelle
I
Madelaine
Martine
M
Bagot
Maxime
M
Battistella
Raphael
R
Porcher
Samia
S
Mourah
Celeste
C
Lebbé
D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015331:Cohort Studies; D057176:Compassionate Use Trials / Q000331:legislation & jurisprudence; D017277:Drug Approval / Q000331:legislation & jurisprudence; D005260:Female; D005602:France; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects; D016019:Survival Analysis; D000077484:Vemurafenib
D000970:Antineoplastic Agents; D007211:Indoles; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf