|| Skin Cancer
|| Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation
| Mode of Action
|| Kinase inhibitor (chemotherapy)
| Approval Status
|| EMA approved (EU); FDA approved (USA); TGA approved (AUS)
|| 20 mg
Who is cobimetinib for?
Cotellic (cobimetinib) is indicated in combination with vemurafenib for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation. The presence of BRAF V600E or V600K mutation in tumour samples needs to be confirmed prior to initiation of treatment 
Complete information about cobimetinib dosage and administration can be found here 
The standard dosage is:
Consult your treating doctor for personalised dosing.
- 60 mg orally once daily for the first 21 days of each 28-day cycle until disease progression or unacceptable toxicity
- Confirm the presence of BRAF V600E or V600K mutation in tumour sample prior to initiation of treatment
What is cobimetinib and how does it work?
Cobimetinib is a cancer medicine used to treat adults with unresectable or metastatic melanoma with a BRAF V600E or V600K Mutation.The active substance in Cotellic, cobimetinib, is a kinase inhibitor. In melanoma with the BRAF V600 mutation, an abnormal form of the protein BRAF is produced, which switches on a protein (MEK), involved in stimulating normal cell division. This encourages the cancer to develop by allowing uncontrolled division of the cancer cells. By blocking this protein cobimetinib slows down the growth and spread of the cancer. Cobimetinib is only given to patients whose melanoma is caused by the BRAF V600 mutation and must be used in combination with the BRAF inhibitor vemurafenib . Vemurafenib is an anticancer medicine that has been widely approved (e.g. by FDA since 2011 , EMA since 2012 , and TGA since 2012 .
What is cobimetinib's approval status?
Cobimetinib was approved by:
The approvals were based on a study (coBRIM) involving 495 patients with BRAF V600 positive unresectable locally advanced or metastatic melanoma. Participants received either vemurafenib plus placebo or vemurafenib plus cobimetinib. The evaluation was primarily based on the progression free survival (PFS). Secondary efficacy endpoints included overall survival (OS), objective response rate (ORR), and duration of response (DoR) . The PFS is the length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse . The OS is the time from the start of the study to the death of the patient . The ORR is the portion of patients with a tumour size reduction of a predefined amount for a minimum time period . The DoR is the time from documentation of tumour response to disease progression .Patients taking cobimetinib plus vemurafenib (N = 247) resulted in a median PFS of 5 months longer than those taking vemurafenib plus placebo (N = 248) (12.3 months (95 % CI 9.5, 13.4) vs. to 7.2 months (95% CI 5.6, 7.5) ). The median OS in the cobimetinib cohort was 22.3 months (95 % CI 20.3, Not Evaluable) vs 17.4 (CI 95 % 15.0, 19.8) . The ORR was 69.6 % (95 % CI 63.5 %, 75.3 %) with cobimetinib and 50.0 % (95 % CI 43.6 %, 56.4 %)  without. The median DoR was 13 months (95 % CI 11.1, 16.6)  when cobimetinib was included in the treatment and 9.2 months (95 % CI 7.5, 12.8)  for patients that took vemurafenib plus placebo.
- FDA (USA) on November 10, 2015 
- EMA (EU) on November 20, 2015 
- TGA (AUS) on April 5, 2016 .
EMA. Human Medicines: Cotellic (cobimetinib), 10/12/2015 (last update: 27/07/2016), cited on 16/03/2017. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/003960/human_med_001925.jsp&mid=WC0b01ac058001d124
Summary of Product Characteristics [FDA]: Cotellic (cobimetinib), Genentech, Nov 2015. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206192s000lbl.pdf
Summary of Product Characteristics [TGA]: Cotellic (cobimetinib), Roche Products Pty Ltd., Apr 2016. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2016-PI-01660-1&d=2017031416114622483
Summary of Product Characteristics [EMA]: Cotellic (cobimetinib), Roche Ltd., Nov 2015. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003960/WC500198563.pdf
Drugs.com. Vemurafenib, (last updated: 01/06/2017), cited on 16/03/2017. https://www.drugs.com/mtm/vemurafenib.html#drug-info-approval
EMA. Human Medicines: Zelboraf (vemurafenib), 19/03/2012 (last update: 30/03/2017), cited on 16/03/2017. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002409/human_med_001544.jsp&mid=WC0b01ac058001d124
Summary of Product Characteristics [TGA]: Zelboraf (vemurafenib), Roche Products Pty Ltd., Sep 2016. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2012-PI-01949-3
FDA News Release: FDA approves Cotellic as part of combination treatment for advanced melanoma. 10/11/2015. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm471934.htm
NIH National Cancer Institute: NCI Dictionary of Cancer Terms: progression-free survival. Cited on 16/03/2017 https://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=44782
Pazdur R. Endpoints for assessing drug activity in clinical trials. The Oncologist. 2008 Apr; 13(2):19–21. http://theoncologist.alphamedpress.org/content/13/suppl_2/19.full.pdf+html
Biooncology.com. Efficacy endpoints in oncology clinical trials. Cited on 16/03/2017. https://www.biooncology.com/clinical-trials/efficacy-endpoints.html
Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Medicine information contained herein may be time sensitive. The absence of a warning for a given medicine or combination thereof in no way should be construed to indicate that the medicine or combination is safe, effective or appropriate for any given patient. Always consult your treating physician before starting a course of treatment.