Patterns of response and progression in patients with BRAF-mutant melanoma metastatic to the brain who were treated with dabrafenib.
BACKGROUND
Dabrafenib has activity in patients with brain metastases, but little is known of the relative efficacy of treatment within and outside the brain. This study sought to examine the intracranial (IC) and extracranial (EC) patterns of response and progression in patients with active melanoma brain metastases treated with dabrafenib.


METHODS
Clinicopathologic parameters were collected on patients with active brain metastases enrolled in the phase 1 and 2 studies of dabrafenib at a single institution. RECIST (Response Evaluation Criteria In Solid Tumors) response and progression-free survival (PFS) were prospectively assessed by disease site (IC versus EC). Treatments received after disease progression were also assessed.


RESULTS
A total of 23 patients were studied. Response rates were similar in IC (78%) and EC (90%) sites (P = .416). IC and EC response was concordant in 71% of patients. Median site-specific PFS was identical in both IC and EC sites (23.6 weeks, P = .465), and exceeded whole-body PFS determined by RECIST (16.3 weeks). Of 20 patients with progressive disease (PD), 6 had IC PD only, 6 had EC PD only, and 8 had PD in both sites. In those with isolated intracranial PD, 5 of 6 underwent local therapy to the brain and continued on dabrafenib longer than 30 days.


CONCLUSIONS
IC and EC melanoma metastases respond similarly to dabrafenib. There is no dominant site or pattern of disease progression in patients with brain metastases treated with dabrafenib. Salvage local therapy is possible in most patients after IC disease progression, with ongoing dabrafenib treatment possible in a subset of patients.
Westmead Hospital, Westmead, Australia; Melanoma Institute Australia, Sydney, Australia.
Mary W F
MW
Azer
Alexander M
AM
Menzies
Lauren E
LE
Haydu
Richard F
RF
Kefford
Georgina V
GV
Long
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000556:secondary; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D010091:Oximes / Q000008:administration & dosage*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016896:Treatment Outcome
D007093:Imidazoles; D010091:Oximes; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C561627:dabrafenib
BRAF inhibitor; brain metastases; dabrafenib; melanoma; progression; response