BRIM 8

BRIM8: A phase III, randomized, double-blind, placebo-controlled study of vemurafenib adjuvant therapy in patients with surgically resected, cutaneous BRAF-mutant melanoma at high risk for recurrence (NCT01667419).

Important results for a patients with a high risk of recurrence- so that is Stage 3- whose tumours carry the BRAF mutation.

Standard of care- wide resection and lymph node removal, sometimes Interferone.

Cohort 1

Stage IIC, IIIA, IIIB and 

Cohort 2

IIIC

who wants placebo on a trial today?

DFS primary endpoint

Cohort 1
median 24 placebo
40 Vemurafenib

Cohort 2
placebo 7.7
Vem 13.3

'Number of events were needed- WHAT?!'



At 1 year:

placebo 78.9%
Vem 58%

but 46.3 vs 47.45 at 2 years

BUT in Stage IIC-IIIB

Distant free survival

pic here 

sigh- pooled analysis even if specified.....only looks good because of the early stage patients (IIC- IIIB)

Side effects-

57% Grade 3-4 toxicity and one death

Overall- as seen previously in Stage 4, also pyrexia

Conclusion: provides OS benefit for IIC-IIIB but not IIIC where it only prolongates time till progression.

Background: Approximately 50% of melanomas carry a mutation in the BRAF gene. The oral BRAF inhibitor vemurafenib (VEM) has demonstrated meaningful clinical benefit in BRAFV600 mutation-positive, locally advanced/unresectable or metastatic melanoma. For patients (pts) with resected melanoma, interferon alfa-2b represents the only widely approved adjuvant therapy; however, its use is limited by a modest improvement in disease recurrence and a high incidence of severe adverse effects that lead to treatment discontinuation in up to a third of pts. BRIM8 is a phase III, international, multicenter, double-blind, randomized, placebo-controlled study designed to evaluate the safety and efficacy of VEM in pts with resected cutaneous melanoma at high risk (>50%) for recurrence (stage IIC and III disease). Methods: Pts aged ≥18 yrs with histologically confirmed stage IIC or III BRAFV600mutation-positive (by cobas testing) melanoma of cutaneous origin that has been completely resected are eligible. Pts without clinical or radiologic evidence of regional lymph node involvement must undergo sentinel lymph node biopsy, and those with evidence of regional or sentinel lymph node involvement must undergo complete regional lymphadenectomy. Pts with a history of systemic therapy for treatment or prevention of melanoma (including interferon alfa-2b) are ineligible. Two cohorts (C) will enroll ~ 725 pts: C1—500 pts with completely resected stage IIC, IIIA (one or more nodal metastasis >1 mm in diameter, per Rotterdam classification), or IIIB cutaneous melanoma; C2—225 pts with stage IIIC cutaneous melanoma. Pts will be randomized 1:1 to receive VEM (960 mg bid) or placebo for 52 weeks with randomization stratified by pathologic stage and region (C1) and by region (C2). Primary efficacy outcome measure is investigator-assessed disease-free survival. Secondary efficacy outcome measures include overall and distant metastasis-free survival. Safety, pharmacokinetic, and pt-reported outcomes will also be assessed. As of 13 Jan 2014, 179/196 sites are active and 154 pts have been randomized (C1: 89; C2: 65). Clinical trial information: NCT01667419.