Safety information
Adverse reactions reported in the coBRIM trial1,3
These adverse reactions occurred in ≥20% (all Grades) of patients receiving COTELLIC® + ZELBORAF® in coBRIM.
COTELLIC + ZELBORAF (n=247) | Placebo + ZELBORAF (n=246 ) | |||
All Grades (0/o) |
Grades 3-4a (0/o) |
AllGrades (0/o) |
Grades 3-4a (0/o) | |
Adverse event | ||||
Rashb | 73 | 17 | 68 | 16 |
Diarrhoea | 61 | 7 | 33 | 1 |
Nausea | 41 | 1 | 25 | 1 |
Arth ralgia | 38 | 3 | 42 | 5 |
Fat igue | 37 | 5 | 33 | 3 |
Blood CPK level increase | 35 | 12 | 3 | < 1 |
Photosensitivity react ion | 34 | 3 | 20 | 0 |
Pyrexia | 29 | 1 | 24 | 0 |
Serous ret inopathyc | 27 | 3 | 4 | 0 |
Vomiting | 26 | 2 | 14 | 1 |
ALT concent ration increase | 26 | 1 1 | 18 | 6 |
AST concentratio n increase | 24 | 9 | 13 | 2 |
GGT concentration increase | 22 | 15 | 18 | 10 |
Dec reased appetite | 20 | 0 | 20 | < 1 |
Alopecia | 17 | < 1 | 31 | < 1 |
Dec reased ej ection f ractiond | 12 | 2 | 5 | 1 |
Hyperkeratosi | 10 | < 1 | 27 | 3 |
QT prolongatio nd | 5 | 1 | 5 | 1 |
Cutaneous squamo us celld | 4 | 4 | 13 | 13 |
Keratoacanthomad | 2 | 1 | 9 | 9 |
Laboratory abnormalities | ||||
ALT concentration increase | 26 | 1 1 | 18 | 6 |
AST concentration increase | 24 | 9 | 13 | 2 |
GGT concentration increase | 22 | 15 | 18 | 10 |
Blood CPK level increase | 35 | 12 | 3 | < 1 |
No filter results
ALT=alanine aminotransferase; AST=aspartate aminotransferase; CPK=creatine phosphokinase; GGT=γ-glutamyltransferase
aThe intensity of clinical adverse events graded by the Common Terminology Criteria for Adverse Events v4.0 (CTC-AE).
b Includes preferred terms rash, rash maculopapular, erythema, dermatitis acneiform, folliculitis, rash macular, rash papular, rash erythematous, acne, dermatitis, rash pruritic, furuncle, rash generalised, dermatitis allergic, rash follicular, rash pustular, dermatitis exfoliative, generalised erythema, rash morbilliform, and drug eruption
c Includes preferred terms chorioretinopathy, retinal detachment, detachment of retinal pigment epithelium, macular oedema, macular fibrosis, retinal disorder, retinopathy, subretinal fluid, and detachment of macular retinal pigment epithelium
d Other selected adverse events based on known association with BRAF or MEK inhibition
- Adverse reactions of ZELBORAF® that occurred at a lower rate in patients receiving COTELLIC® + ZELBORAF® were alopecia (14% difference between treatment arms), hyperkeratosis (17% difference between treatment arms) and arthralgia (4% difference between treatment arms)
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at: https://www.roche.com/products/local_safety_reporting.htm
Please see both the COTELLIC® Summary of Product Characteristics and ZELBORAF® Summary of Product Characteristics for additional important safety information.
References
1. COTELLIC® - Summary of Product Characteristics; available at: https://www.ema.europa.eu/en/documents/product-information/cotellic-epar-product-information_en.pdf 2018.
2. ZELBORAF® - Summary of Product Characteristics; available at: https://www.ema.europa.eu/en/documents/product-information/zelboraf-epar-product-information_en.pdf 2018.
3. Ascierto PA, McArthur GA, Dréno B, et al. Cobimetinib combined with vemurafenib in advanced BRAF(V600)-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial. Lancet Oncol. 2016;17:1248–1260.
4. Larkin J, Ascierto PA, Dréno B, et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med. 2014;371:1867–1876.