1124P - An open-label, multicentre safety study of vemurafenib in patients with metastatic melanoma

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Anticancer agents
Skin cancers
Biological therapy
Presenter Christian Blank
Authors C. Blank1, M. Del Vecchio2, P.A. Ascierto3, P. Queirolo4, A. Hauschild5, A. Arance6, M. Brown7, L. Mitchell8, L. Veronese8, J. Larkin9
  • 1Medical Oncology, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 2Oncologia Medica, Instituto Nazionale dei Tumori, Milan/IT
  • 3Unit Of Medical Oncology And Innovative Therapy, Istituto Nazionale Tumori Fondazione G. Pascale, Naples/IT
  • 4National Institute For Cancer Research, San Martino Hospital, Genova/IT
  • 5Dept. Of Dermatology, Universitätsklinikum Schleswig-Holstein, Kiel/DE
  • 6Medical Oncology, Hospital Clinic, Barcelona/ES
  • 7Oncology, Royal Adelaide Hospital Cancer Centre, Adelaide/AU
  • 8., F. Hoffmann-La Roche Ltd, Basel/CH
  • 9Department Of Medicine, Royal Marsden Hospital, SW3 6JJ - London/UK



Vemurafenib, a BRAF inhibitor, is associated with improved progression-free survival and overall survival in patients (pts) with BRAFV600-mutant metastatic melanoma (mM). Here we present findings from a safety study of vemurafenib in pts with unresectable Stage IIIC/IV BRAFV600-positive mM.


Pts with untreated or previously treated Stage IIIC/IV BRAFV600 mutation-positive (cobas® 4800 BRAF V600 Mutation Test) melanoma were enrolled. Pts received continuous oral vemurafenib 960 mg bid. Primary study endpoint was safety; efficacy (RECIST V 1.1) was a secondary endpoint.


Of 5273 screened pts (Mar 2011–Feb 2012), 2353 (45%) were enrolled and 2096 received ≥1dose of vemurafenib. Median age was 54 (16–95 years), 56% were male. Median time since first mM diagnosis was 6.4 months. Most pts were Stage IV (84%); 47.1% M1c, 2% Stage IIIC (stage not reported for 14% of pts). At baseline, 87% of pts had ECOG PS 0/1, 11% ECOG PS ≥2; 24% had brain metastases and 37% had elevated LDH. Most pts had received prior systemic therapy (60%) including ipilimumab (10%), MEK and BRAF inhibitors (3%). At data cut-off (29 Feb 2012), median treatment duration was 3.1 months (<1–11.2 months). Of 2096 pts, 1792 (86%) have reported AEs, 76% were related to vemurafenib, 32% Grade 3 and 2.3% Grade 4. Most common Grade 3/4 AEs were rash (2.8%), arthralgia (2.5%), fatigue (1.3%) and cutaneous squamous cell carcinoma/keratoacanthoma (6.0%). Most common AEs (>10%) of any grade were arthralgia (30.7%), rash (25.6%), fatigue (19.6%), alopecia (15.6%), nausea (15%) and photosensitivity (11%), and were similar irrespective of brain metastases and ECOG PS. AEs caused treatment interruption in 492 (23.5%) pts. Of 774 pts (37%) who discontinued treatment, most withdrew due to progressive disease (71%) or death (14%) but 6% had AEs (most commonly general physical deterioration). Tumour assessments at Week 8 of treatment were available for 1356/2096 (65%) pts; 60% of pts achieved a CR or PR; 31% had SD.


In a setting representative of routine clinical practice, vemurafenib is well tolerated and both safety profile and activity resemble the Phase I–III data, although this analysis is limited by the study duration.


C. Blank: Financial disclosure: Roche global steering committee, Roche NL presentations, conference travel, Novartis NL: conference travel, advisory board; MedImmune: research grant; BMS: advisory board, clinical research funding.

M. Del Vecchio: Consultant or Advisory Role: Merck/Schering-Plough (U); Research Funding: Celgene, Novartis, Roche.

P.A. Ascierto: Consultant for MSD; Advisory role for BMS, MSD, Roche-Genetech, GSK, Amgen, Celgene, Medimmune, Novartis; received honoraria from BMS, MSD, and Roche-Genentech.

P. Queirolo: Advisory Board of Bristol Myers Squibb, Roche-Genentech, GSK, MSD and received honoraria from Brystol Myers Squibb and Roche-Genentech.

A. Hauschild: Honoraria for ad- board membership, and payments for lectures/speakers bureaus from Amgen, AstraZenica, Biovex, BMS, Boehringer, Ingelheim, Celgene, Eisai, GSK, IGEA, Lilly, Medac, MelaSciences, MSD?Merck, Novartis, Roche Pharma, SOBI, Vical, Janssen.

A. Arance: Steering committee of this safety study (Roche).

M. Brown: Membership of a Roche Melanoma Advisory Board.

L. Mitchell: Full-time employee at F. Hoffmann-la-Roche

L. Veronese: Full-time employee at F. Hoffmann-la-Roche.

All other authors have declared no conflicts of interest.