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coBRIM showed that adding cobimetinib to vemurafenib gives people with BRAF-mutant melanoma about five more months before the disease grows and about five more months of life.
coBRIM randomised 495 patients with untreated BRAF V600 metastatic melanoma to vemurafenib with cobimetinib or vemurafenib with placebo. It was the second phase 3 trial of a BRAF plus MEK doublet and used the first approved BRAF inhibitor as its backbone.
Median progression-free survival was 12.3 months with the combination against 7.2 months (hazard ratio 0.58) in the updated analysis (Lancet Oncology 2016), and median overall survival 22.3 months against 17.4 months (hazard ratio 0.70). Serous retinopathy, raised creatine kinase and photosensitivity were the notable toxicities; secondary skin cancers were less frequent than with vemurafenib alone.
The result led to approval of cobimetinib in late 2015 and, with COMBI-d and COMBI-v, settled that the doublet rather than a single BRAF inhibitor is the standard. The vemurafenib-cobimetinib backbone was later used in IMspire150 to test the addition of atezolizumab.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
495 enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Progression-free survivalprimary | Vemurafenib + cobimetinib | 247 | 12.3 months | 0.58 | - | link |
| Vemurafenib + placebo | 248 | 7.2 months | ||||
| Overall survival | Vemurafenib + cobimetinib | 247 | 22.3 months | 0.7 | - | link |
| Vemurafenib + placebo | 248 | 17.4 months |
A second publication from the coBRIM trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.
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.
Shares Paolo A. Ascierto, Test intermittent dosing of targeted drugs to delay resistance, with honest priors, Vemurafenib, BRAF V600-mutant melanoma.
Shares Test intermittent dosing of targeted drugs to delay resistance, with honest priors, MEK1/2, BRAF V600-mutant melanoma, Advanced melanoma (unresectable stage III and stage IV).
Shares Cobimetinib, BRAF V600-mutant melanoma, Advanced melanoma (unresectable stage III and stage IV), Melanoma.
Shares Cobimetinib, Vemurafenib, BRAF, Melanoma.
Shares Vemurafenib, BRAF V600-mutant melanoma, BRAF, Melanoma.
Shares Cobimetinib, MEK1/2, Vemurafenib, BRAF V600-mutant melanoma.
Shares Cobimetinib, Vemurafenib, BRAF V600-mutant melanoma, Roche / Genentech.
Shares Test intermittent dosing of targeted drugs to delay resistance, with honest priors, Vemurafenib, BRAF V600-mutant melanoma.