Given the positive findings from the coBRIM phase III study having assessed cobimetinib (C) plus vemurafenib (V) in patients (pts) with BRAF V600 mutation-positive unresectable locally advanced or metastatic melanoma, a Temporary Authorization for Use (TAU) program (pre-approval access to new treatment options where unmet medical need exists) has been settled in France for cobimetinib from 27 Apr 2015 to 04 Jan 2016.
Analysis was performed in pts with approved treatment-access delivered within TAU. Specific forms had to be completed at C initiation (in combination with V) and monthly after first treatment intake. All adverse events (AEs) had to be reported during pts' follow-up.
A total of 376 pts had approved early access to the combined therapy (C plus V). Following baseline data were available for 328 pts (87%). Mean age was 57 ± 15 years and 59% were male. A total of 290 pts (89%) had stage IV melanoma (M1a: 11%, M1b: 13%, M1c: 64%) and 79 pts (24%) presented with brain metastasis. During follow-up, 280 AEs were reported in 134 of 376 pts (36%), including 208 (74%) C-related AEs reported in 108 pts (29%) and/or 160 (57%) V-related AEs reported in 82 pts (22%). Among the 101 (36%) serious AEs (SAEs) reported in 63 pts (17%), 67 SAEs (24%) reported in 42 pts (11%) were assessed as related to C. Twenty-two AEs (8%) reported in 12 pts (3%) led to permanent C discontinuation. Fifty-three predefined specific AEs (19%) were reported in 49 pts (13%): 23 increased creatine phosphokinase (including 2 SAEs), 12 photosensitivity reactions (7 SAEs), 7 retinal detachments (3 SAEs), 7 renal failures (3 SAEs), and 4 left ventricular ejection fraction decreases (1 SAE). No squamous cell carcinoma nor C-related death were reported during follow-up.
These real-life data from this French TAU program are consistent with safety data collected during clinical development program and showed no new safety signal for C when combined with V to treat pts with unresectable or metastatic melanoma.
Clinical trial identification
Not applicable as this is not a clinical trial.
Abstract is about french compassionate use data TAU. (Protocol number ML29897 dated on 27th april 2015.
Legal entity responsible for the study
N. Meyer: Financial interest for professor Nicolas Meyer, in Melanoma, with differents pharmaceuticals companies: -Roche -Novartis -BMS -MSD -Amgen -GSK. D-M. Anne-Bénédicte: Financial interest for doctor Duval Modeste with differents pharmaceuticals laboratories: -Roche -Novartis -BMS -Abbvie -Janssen Cilag -Pfizer. B. Dreno: Finantial interest for professor Dreno Brigitte with differents pharmaceuticals companies: -Roche -Novartis -BMS -Amgen. C. Lebbe: Financial interest in Melanoma for Doctor Celeste Lebbe: -Roche -Novartis -BMS -MSD -Amgen. O. Zehou: Financial interest for doctor Ouidad Zehou in melanoma, with other pharmaceuticals laboratories: Roche Novartis BMS. A. Gorana: Financial interest for Adrian Gorana: He is doctor in drug monitoring for Roche S.A.S. M. Mouri: Financial interest for Mehdi Mouri: He works for Roche S.A.S, he is doctor and medical responsible in dermatology and hematology. A. Bardet: Financial interest in Melanoma for Aurélie Bardet: She is Bio-statistician for Roche S.A.S. M. Moreau: Project manager for Roche S.A.S. C. Mateus: Financial interest for doctor Christina Mateus in melanoma with other Pharmaceuticals companies: -Roche