Patterns of response and progression in patients with BRAF-mutant melanoma metastatic to the brain who were treated with dabrafenib

Authors

  • Mary W. F . Azer MB ChB,

    1. Westmead Hospital, Westmead, Australia
    2. Melanoma Institute Australia, Sydney, Australia
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    • The first 2 authors are equal contributors to this study.

  • Alexander M. Menzies MBBS,

    1. Melanoma Institute Australia, Sydney, Australia
    2. The University of Sydney, Sydney, Australia
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    • The first 2 authors are equal contributors to this study.

  • Lauren E. Haydu BSCHE,

    1. Melanoma Institute Australia, Sydney, Australia
    2. The University of Sydney, Sydney, Australia
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  • Richard F. Kefford MBBS, PhD,

    1. Westmead Hospital, Westmead, Australia
    2. Melanoma Institute Australia, Sydney, Australia
    3. The University of Sydney, Sydney, Australia
    4. Westmead Institute for Cancer Research, Westmead, Australia
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  • Georgina V. Long MBBS, PhD

    Corresponding author
    1. Melanoma Institute Australia, Sydney, Australia
    2. The University of Sydney, Sydney, Australia
    3. Westmead Institute for Cancer Research, Westmead, Australia
    • Corresponding author : Georgina Long, PhD, MBBS, Melanoma Institute Australia and The University of Sydney, 40 Rocklands Road, North Sydney, NSW 2060, Australia; Fax: (011) +61 2 9954 9290; georgina.long@sydney.edu.au

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  • This study was presented in part at the 2012 American Society of Clinical Oncology Annual General Meeting, Chicago, Illinois, and the 2012 Medical Oncology Group Australia Annual Scientific Meeting, Brisbane, Australia.

  • We thank the Westmead melanoma and clinical trials team: Arthur Clements, Lydia Visintin, Rebecca Hinshelwood, Amie Cho, Vicky Wegener, Andrea Del Pilar Forero V., Jacob Cunningham, Natalie Byrne, Katherine Carson, Joanna Jackson, Medhia Survery, Meenal Rai, Larry Hernandez; and Angela Hong, Gerald Fogarty, Brindha Shivalingham, Peter Lebowitz, Jeffrey Legos (GlaxoSmithKline), Michael Streit (GlaxoSmithKline), and Vicki Goodman (GlaxoSmithKline) for their assistance with this work.

Abstract

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. Cancer 2014;120:530–536. © 2013 American Cancer Society.

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