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Sub-category:
Melanoma
Category:
Melanoma
Meeting:
2008 ASCO Annual Meeting
Abstract No:
9072
Citation:
J Clin Oncol 26: 2008 (May 20 suppl; abstr 9072)
Author(s):
C. J. Min, L. F. Liebes, J. Escalon, A. Hamilton, H. Yee, M. T. Buckley, J. J. Wright, I. Osman, D. Polsky, A. C. Pavlick
Abstract:
Background: This is a completed outcome analysis of a phase II trial of S in MM which aimed to determine if treatment (tx) with S altered tumor proliferation,and induced differential anti-tumor responses (resp) in wt or mutB-Raf MM. Mutation detection was performed using a newly developed fluorescent based mutant-specific PCR assay (MS-PCR). Methods: Biopsy (bx)-accessible, untreated MM with measurable disease (RECIST). Stratification:Tumor BRAF status at codon V600 by routine PCR sequencing and MS-PCR. Tx: BAY 400 mg po BID D1-28 q4w. Serial studies: Repeat bx on day 28 for ki-67, cyclin-D1 and ERK; serum collagen cryptic epitopes (epi); re-imaging every 2 cycles; pts treated until progression (PD). Follow-up analysis done on trial completion. Results: 37 pts (11-M1a, 10-M1b, 16-M1c) enrolled. Routine BRAF sequencing yielded 32 wt and 5 mut. MSPCR yielded 22 wt and 15 mut. Median age: 68 (range 22-91); LDH > 1.5 x nl in 12. Toxicity: Gr I diarrhea (7), alopecia (4), rash (6), mucositis (muc) (4), nausea (4), pain (4), hand-foot(h/f) (2); Gr II HTN (4), fatigue (2), muc (1), rash (3), pain (3), h/f (2); Gr III h/f (1), rash (1), fatigue (1), intestinal perforation (1). Tox identical in both groups. Resp: mutBRAF -1 PR (nodes and subcutaneous masses) and 4 PD; wtBRAF -2 PR, 6 SD and 12 PD after 2 cycles. Assessment incomplete in 12 ( 8 early PD, 1 tox drop-out, 1 withdrew prior to tx and 1 no eval tumor). Epi decreased with resp lasting 16-32 w; biopsies demonstrated down regulation of tumor ki-67, erk and cyclin-D1 in PRs and SD. 6 pts with nodular mel of head or acral, all mutBRAF died of brain mets in < 9m. 20 pts with superficial spreading or lentigo maligna died from PD between 5 and 14 months. 11 remain alive with disease- 5wt (1 nodular) and 6mutBRAF (f/u 6-28 m). Conclusions: S monotherapy is minimally active with few short-term resp in both mu and wt B-Raf MM. Down- regulation of proliferation markers was demonstrated, and MS-PCR improved the detection of muBRAF. In this small pt subset, it appears that nodular melanomas of the head or acral origin, are predominantly mutBRAF and quickly metastasize to brain. Supported by NCI N01-CM17103 and TRI 25XS091.
Abstract Disclosures
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy
and are designated with a caret symbol (^) here and in the print version.
 Associated Presentation(s):
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1. Phase II trial of sorafenib (S [BAY 43-9006]) in metastatic melanoma (MM) including detection of BRAF with mutant specific-PCR (MS-PCR) and altered proliferation pathways-final outcome analysis.
Meeting:
2008 ASCO Annual Meeting
Presenter:
Christina J Min, MD
Session:
Melanoma
(General Poster Session)
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Other Abstracts in this Sub-Category:
Abstracts by C. J. Min :
Presentations by C. J. Min :
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1. Phase II trial of sorafenib (S [BAY 43-9006]) in metastatic melanoma (MM) including detection of BRAF with mutant specific-PCR (MS-PCR) and altered proliferation pathways-final outcome analysis.
Meeting:
2008 ASCO Annual Meeting
Presenter:
Christina J Min, MD
Session:
Melanoma
(General Poster Session)
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More...
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Educational Book Manuscripts by C. J. Min :
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