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Poster display session

4074 - Hybrid-capture based genomic profiling identifies BRAF V600 and non-V600 alterations in melanoma samples negative by prior testing

Date

10 Sep 2017

Session

Poster display session

Presenters

Lise Boussemart

Citation

Annals of Oncology (2017) 28 (suppl_5): v428-v448. 10.1093/annonc/mdx377

Authors

L. Boussemart1, A. Wang2, M.K.K. Wong3, J.S. Ross4, P.J. Stephens5, S.M. Ali6, J. Sosman7, J.M. Mehnert8, G. Daniels9, K. Kendra10, A.B. Schrock6, V.A. Miller11

Author affiliations

  • 1 Department Of Dermatology, Pontchaillou Hospital, CHU de Rennes, 35000 - Rennes/FR
  • 2 Clinical Development, Foundation Medicine, Inc., 02141 - Cambridge/US
  • 3 Department Of Melanoma Medical Oncology, MD Anderson Cancer Center, 77030-4095 - Houston/US
  • 4 Pathology, Albany Medical Center, 12208 - Albany/US
  • 5 R & D, Foundation Medicine, 02141 - Cambridge/US
  • 6 Clinical Development, Foundation Medicine, MA 02141 - Cambridge/US
  • 7 Oncology, Northwestern University, Chicago/US
  • 8 Division Of Medical Oncology, The Cancer Institute of New Jersey, 8903 - New Brunswick/US
  • 9 Medicine, University of California San Diego, La Jolla/US
  • 10 Oncology, The Ohio State University, Columbus/US
  • 11 Medical Affairs, Foundation Medicine, 02141 - Cambridge/US
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Resources

Abstract 4074

Background

BRAF and MEK inhibitors are approved for V600-mutated melanoma, and response rates of up to 70% are seen for patients with V600 mutations. Responses to targeted therapies have also been observed for a variety of non-V600 BRAF alterations. Thus, sensitive, accurate, and broad detection of BRAF alterations is critical to match patients with available targeted therapies.

Methods

Pathology reports were reviewed for 385 consecutive melanoma cases (Mar 2016 - Mar 2017) with BRAF mutations or rearrangements identified using a hybrid-capture based next generation sequencing (NGS) assay during the course of clinical care.

Results

Records of prior BRAF molecular testing were available for 79 (21%) cases, utilizing PCR (n = 30), Sanger sequencing (n = 13), IHC (n = 10), non-hybrid capture based NGS (n = 9), or other or unspecified methodology (n = 17). Of cases with BRAF V600 mutations 11/57 (19%) with available data were negative by prior BRAF testing, including 2/11 (18%) with confirmation that the same biopsy was tested. In cases with BRAF V600 mutations, there was no significant difference in mutant allele frequencies (median 35% vs. 40%, p = 0.25) or percentage of tumor nuclei (median 50% for both, p = 0.97) between samples with prior negative and prior positive results. Prior negative results were also identified in 16/20 (80%) cases with non-V600 mutations, two of which harbored multiple BRAF alterations [K601E (4), D594A/G/N (4), S467L (2), L584F (2), G464V, G466V, G469V, E586K, N581I, L597Q, A589_T599insT]. Two of 2 (100%) cases with activating BRAF fusions also had prior negative BRAF results. Clinical outcomes for a subset of patients will be presented.

Conclusions

Despite approved companion diagnostics, significant variability exists in methods for BRAF testing in the clinical setting. Hybrid-capture based NGS identifies diverse activating mutations and fusions, including BRAF V600E, in a significant fraction of cases for which prior BRAF testing returned negative results. Given the proven clinical benefit in patients with BRAF alterations treated with match targeted therapies, hybrid-capture based NGS should be considered for patients with metastatic melanoma, particularly if other testing is negative.

Clinical trial identification

Legal entity responsible for the study

Foundation Medicine, Inc.

Funding

Foundation Medicine, Inc.

Disclosure

A. Wang, J.S. Ross, P.J. Stephens, S.M. Ali, A.B. Schrock, V.A. Miller: Employee with stock ownership in Foundation Medicine, Inc. All other authors have declared no conflicts of interest.

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