coBRIM
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.
Overview
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.
- Median 12.3 vs 7.2 months with Vemurafenib + cobimetinib compared with Vemurafenib + placebo; about 5.1 months longer for half the group.
- A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
- Put another way, the treated group had about 42 percent lower chance of the event at any given time (hazard ratio 0.58).
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- Median 22.3 vs 17.4 months with Vemurafenib + cobimetinib compared with Vemurafenib + placebo; about 4.9 months longer for half the group.
- A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
- Put another way, the treated group had about 30 percent lower chance of the event at any given time (hazard ratio 0.7).
- Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
- These results apply to the people the trial enrolled: Untreated unresectable or metastatic BRAF V600-mutant melanoma: vemurafenib plus cobimetinib versus vemurafenib plus placebo. People in a different situation may not see the same effect.
- The trial selected people by a biomarker (BRAF); the result should not be assumed for people whose cancer does not have it.
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 participants 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 |
Similar pages
not linked directly; found by shared links- TrialCOLUMBUS
Shares Paolo A. Ascierto, Vemurafenib, BRAF V600-mutant melanoma, Advanced melanoma (unresectable stage III and stage IV).
- PersonGrant McArthur
Shares Cobimetinib, Vemurafenib, BRAF, Melanoma.
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Shares Cobimetinib, Vemurafenib, MEK1/2, BRAF V600-mutant melanoma.
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Shares Cobimetinib, BRAF V600-mutant melanoma, Melanoma.
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Shares Vemurafenib, BRAF V600-mutant melanoma, BRAF, Melanoma.
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- TrialDREAMseq (ECOG-ACRIN EA6134)
Shares BRAF V600-mutant melanoma, Advanced melanoma (unresectable stage III and stage IV), BRAF, Melanoma.