# Combined vemurafenib and cobimetinib in BRAF-mutated melanoma

Source: https://onco.cc/key-papers/paper-cobrim-n-engl-j-med-2014/  
OnCo record `paper-cobrim-n-engl-j-med-2014` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Published report from the coBRIM trial registered as NCT01689519, in New England Journal of Medicine (2014), chosen as the most cited paper whose own text cites the registry id.

## Summary

Background: The combined inhibition of BRAF and MEK is hypothesized to improve clinical outcomes in patients with melanoma by preventing or delaying the onset of resistance observed with BRAF inhibitors alone. This randomized phase 3 study evaluated the combination of the BRAF inhibitor vemurafenib and the MEK inhibitor cobimetinib.

Methods: We randomly assigned 495 patients with previously untreated unresectable locally advanced or metastatic BRAF V600 mutation-positive melanoma to receive vemurafenib and cobimetinib (combination group) or vemurafenib and placebo (control group). The primary end point was investigator-assessed progression-free survival.

Results: The median progression-free survival was 9.9 months in the combination group and 6.2 months in the control group (hazard ratio for death or disease progression, 0.51; 95% confidence interval [CI], 0.39 to 0.68; P<0.001). The rate of complete or partial response in the combination group was 68%, as compared with 45% in the control group (P<0.001), including rates of complete response of 10% in the combination group and 4% in the control group. Progression-free survival as assessed by independent review was similar to investigator-assessed progression-free survival. Interim analyses of overall survival showed 9-month survival rates of 81% (95% CI, 75 to 87) in the combination group and 73% (95% CI, 65 to 80) in the control group. Vemurafenib and cobimetinib was associated with a nonsignificantly higher incidence of adverse events of grade 3 or higher, as compared with vemurafenib and placebo (65% vs. 59%), and there was no significant difference in the rate of study-drug discontinuation. The number of secondary cutaneous cancers decreased with the combination therapy.

Conclusions: The addition of cobimetinib to vemurafenib was associated with a significant improvement in progression-free survival among patients with BRAF V600-mutated metastatic melanoma, at the cost of some increase in toxicity. (Funded by F. Hoffmann-La Roche/Genentech; coBRIM ClinicalTrials.gov number, NCT01689519.).

Indexed on Europe PMC as PubMed record 25265494 (DOI 10.1056/nejmoa1408868). Its abstract cites the registry id NCT01689519, which is how it was matched to this trial; no figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: New England Journal of Medicine
- Year: 2014
- DOI: 10.1056/nejmoa1408868
- Authors: Larkin J, Ascierto PA, Dréno B, et al.
- What it means: This is the paper Europe PMC returns for registry id NCT01689519 with the most citations, so it is the natural first reading for anyone following the coBRIM trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
- Caveats: Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.

## Sources

- N Engl J Med 2014: https://doi.org/10.1056/nejmoa1408868
- PubMed: https://pubmed.ncbi.nlm.nih.gov/25265494/
- Europe PMC: https://europepmc.org/article/MED/25265494
- ClinicalTrials.gov NCT01689519: https://clinicaltrials.gov/study/NCT01689519

## Connected records

- trials: [coBRIM](https://onco.cc/trials/cobrim/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

---
JSON: https://onco.cc/api/v1/entities/paper-cobrim-n-engl-j-med-2014.json