Patterns of progression in patients (pts) with V600 BRAF-mutated melanoma metastatic to the brain treated with dabrafenib (GSK2118436)

M. Azer, A. Menzies, L. Haydu, R. Kefford, G. Long

Research output: Contribution to journalMeeting abstractpeer-review

Abstract

Background: Dabrafenib has shown efficacy in patients (pts) with previously untreated brain metastases (BM) but most will progress. We report the pattern of disease progression (DP) in pts with either previously treated (surgery [Sx], stereotactic radiosurgery [SRS], whole brain radiotherapy [WBRT]) or untreated BM on dabrafenib.

Methods: Clinicopathologic parameters were collected on 23 pts enrolled in the brain cohort of the BRF112680 phase I and BRF113929 phase II BM study of dabrafenib at Westmead Hospital between September 2009 and June 2011. Pts with Response Evaluation Criteria in Solid Tumors (RECIST) progressive disease (PD) but ongoing clinical benefit were allowed to continue dabrafenib.

Results: 12 pts (52%) had previously untreated BM and 11 (48%) were
previously treated with evidence of progression prior to dabrafenib. Median overall survival (OS) from study entry (8.4 month [mo], 95% confidence interval [CI] 5.1–11.7), diagnosis of first BM (10.5 mo, 95% CI 8.9–12.2), and stage IV diagnosis (14.1 mo, 95% CI 7.7–20.5) were not different between the two groups. Similarly, progression free survival (PFS) did not differ between groups.

The intracranial (IC) disease control rate (best response of complete response [CR], partial response [PR] and stable disease [SD]) was 92 % (n = 11) and 100% (n = 11) in the untreated and previously treated BM, respectively. Of the 20 pts who had RECIST PD at datacut, 14 pts had IC PD with no pts progressing in new brain lesions alone (see table). At IC PD, 4/14 underwent SRS/Sx, 5/14 WBRT and 5/14 had no salvage local therapy to BM. 9 pts continued dabrafenib beyond IC PD, median 55 days, range 16–273. All measures of baseline disease burden correlated with worse OS, elevated lactate dehydrogenase (LDH) (hazard ratio [HR] 1.003, 95% CI 1.000–1.006, P = 0.050), increased number (no.) of IC lesions (HR 1.044, 95% CI 1.004–1.086, P = 0.031), increased no. extracranial (EC) lesions (HR 1.061, 95% CI 1.021–1.102, P = 0.003) and increased RECIST sum of diameters (SoD) (HR 1.012, 95% CI 1.004–1.019, P = 0.004). High base-line SoD was the only factor that predicted worse RECIST response.

Conclusions: Clinical benefit from dabrafenib does not appear to be influenced by prior local therapies to BM. There was no dominant pattern of progression in pts with BM on dabrafenib, but PD due to new lesions alone is rare. Pts with IC PD may benefit from salvage local therapy and continued dabrafenib. Extent and burden of disease correlates with reduced OS, but not RECIST response.
Original languageEnglish
Pages (from-to)48-48
Number of pages1
JournalAsia-Pacific Journal of Clinical Oncology
Volume8
Issue numberSupplement 2
Publication statusPublished - 31 Jul 2012
Externally publishedYes
EventMedical Oncology Group of Australia Incorporated Annual Scientific Meeting - Brisbane, QLD, Australia
Duration: 8 Aug 201210 Aug 2012

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