1109P - Vemurafenib in BRAFV600 mutated metastatic melanoma (MM): a subanalysis of the Italian population of a global safety study

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anticancer Agents
Skin Cancers
Personalised/Precision Medicine
Basic Principles in the Management and Treatment (of cancer)
Biological Therapy
Presenter Michele Del Vecchio
Citation Annals of Oncology (2014) 25 (suppl_4): iv374-iv393. 10.1093/annonc/mdu344
Authors M. Del Vecchio1, P.A. Ascierto2, M. Mandala3, V. Chiarion Sileni4, M. Maio5, L. Di Guardo6, E. Simeone7, P. Queirolo8
  • 1Medical Oncology, Istituto Nazionale Tumori, 20100 - Milan/IT
  • 2Unit Of Medical Oncoloty And Innovative Therapy, Istituto Nazionale Tumori Fondazione G. Pascale, Napoli/IT
  • 3Oncology And Haematology, Ospedali Riuniti di Bergamo, 24100 - Bergamo/IT
  • 4Medical Oncology, Istituto Oncologico Veneto IOV-IRCCS, IT-35128 - Padova/IT
  • 5Division Of Medical Oncology And Immunotherapy, University Hospital of Siena, Istituto Toscano Tumori, Siena/IT
  • 6Department Of Medical Oncology, National Cancer Institute, Milan/IT
  • 7Oncology, national cancer institute, 80131 - naples/IT
  • 8Department Of Oncology, National Institute for Cancer Research - Genova, Genova/IT



Vemurafenib, a BRAF kinase inhibitor, is effective and safe in MM with BRAF V600 mutation. We describe the ad interim analysis of the Italian cohort of the global safety study on vemurafenib.


Patients with untreated or previously treated BRAFV600 MM received oral vemurafenib 960 mg twice daily until progression or toxicity.


Overall, 385 patients were evaluated; 135 received prior systemic chemotherapy (35%) and 44 (11%) ipilimumab. Forty-eight patients had stage M1a disease, 53 M1b and 280 M1c. Median follow-up was 11.5 mos (95% CI 11.2–11.8). Three hundred and thirty patients (86%) reported at least one adverse event (AE). Common AEs included rash (21%), arthralgia (25%), asthenia (14%), alopecia (13%), nausea (12%). Squamous cell carcinoma was diagnosed in 8 patients (2.1%), keratoacanthoma in 9 (2.3%). Sixteen severe AEs were reported; among these, 3 were related to vemurafenib. Response rate was assessed in 332 patients: 4.2% (n = 14) showed a complete response, 26.2% (n = 87) a partial response and 54.5% (n = 181) stable disease. Median progression free survival (PFS) and overall survival (OS) were 5.9 mos (95% CI: 5.4-6.8) and 16.3 mos (13.4-not reached), respectively. Furthermore, 21.5% of patients (n = 83) had brain metastasis (BM). In this subgroup, median PFS was 4.3 mos (3.6-5.4) and OS was 7.6 mos (6.0-11.1). In patients without BM the median PFS was 6.5 mos (5.7-8.0) and OS was not reached (16.3-not reached). Results according to disease stage at baseline are reported in Table; 146 patients (37.9%) received vemurafenib beyond progression.

Efficacy data according to disease stage.
Disease stage Survival at 12 months (%) [95% CI] Median progression-free survival [95% CI] (months)
M1a 90.5 [81.6-99.4] 12.6 [7.7-Not estimated]
M1b 73.6 [60.6-86.7] 9.6 [6.0-13.2]
M1c 53.6 [46.5-60.7] 5.4 [4.7-5.9]


Vemurafenib appears safe and active in a population of Italian patients with BRAFV600 mutated MM who are representative of routine clinical practice. Although the subgroup analysis is hampered by the low number of patients in each subgroup, our data might suggest that vemurafenib is particularly active in patients without BM and low tumor burden (M1a).


M. Del Vecchio: MDV has been an adviser for Merck, Sharp, and Dohme, and Schering-Plough; received honoraria from Roche, Celgene, and GlaxoSmithKline; and received research funding from Roche, Celgene, GlaxoSmithKline, and Bristol-Myers Squibb; P.A. Ascierto: PAA has received research funding from Bristol-Myers Squibb and has been a consultant or participated on advisory boards for Bristol-Myers Squibb, Roche-Genentech, GlaxoSmithKline, and Novartis; M. Mandala: MM has participated in advisory boards for Roche-Genentech, GlaxoSmithKline, and Bristol-Myers Squibb. AA has received funding for board membership, lectures, and travel expenses from Roche and Bristol-Myers Squibb.;V. Chiarion Sileni: VC-S has received compensation for participation in advisory boards from Bristol-Myers Squibb, Roche-Genentech, and GlaxoSmithKline; P. Queirolo: PQ has served on advisory boards for Roche, GlaxoSmithKline, and Bristol-Myers Squibb. All other authors have declared no conflicts of interest.