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.