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Mol Cancer Ther. 2015 Aug;14(8):1962-71. doi: 10.1158/1535-7163.MCT-15-0153. Epub 2015 Jun 10.

Pilot Trial of Selecting Molecularly Guided Therapy for Patients with Non-V600 BRAF-Mutant Metastatic Melanoma: Experience of the SU2C/MRA Melanoma Dream Team.

Author information

1
Yale Cancer Center, New Haven, Connecticut. Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, Michigan. patricia.lorusso@yale.edu.
2
Yale Cancer Center, New Haven, Connecticut. Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, Michigan.
3
Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, Michigan.
4
Translational Genomics Research Institute, Phoenix, Arizona.
5
Biometrics Research Branch, National Cancer Institute, National Institutes of Health, Rockville, Maryland.
6
University of Michigan Comprehensive Cancer Center (UMCCC), Ann Arbor, Michigan.
7
Mayo Clinic, Rochester, Minnesota.
8
Mayo Clinic, Scottsdale, Arizona.
9
Mayo Clinic, Jacksonville, Florida.
10
Charles A. Sammons Cancer Center/Baylor University Medical Center, Dallas, Texas.
11
Vanderbilt University, Nashville, Tennessee.
12
Memorial Sloan-Kettering Cancer Center, New York, New York.
13
Columbia University, New York, New York.

Abstract

Targeted therapies and immunotherapies have led to significant improvements in the treatment of advanced cancers, including metastatic melanoma. However, new strategies are desperately needed to overcome therapeutic resistance to these agents, as well as to identify effective treatment approaches for cancer patients that fall outside major targetable mutational subtypes (e.g., non-V600 BRAF melanoma). One such strategy is to extend the paradigm of individually tailored, molecularly targeted therapy into a broader spectrum of melanoma patients, particularly those bearing tumors without commonly recognized therapeutic targets, as well as having failed or were ineligible for immunotherapy. In this nontreatment pilot study, next-generation sequencing (NGS) technologies were utilized, including whole genome and whole transcriptome sequencing, to identify molecular aberrations in patients with non-V600 BRAF metastatic melanoma. This information was then rationally matched to an appropriate clinical treatment from a defined pharmacopeia. Five patients with advanced non-V600 BRAF metastatic melanoma were enrolled. We demonstrated successful performance of the following during a clinically relevant time period: patient tumor biopsy, quality DNA/RNA extraction, DNA/RNA-based sequencing for gene expression analysis, analysis utilizing a series of data integration methodologies, report generation, and tumor board review with formulated treatment plan. Streamlining measures were conducted based on the experiences of enrolling, collecting specimens, and analyzing the molecular signatures of patients. We demonstrated the feasibility of using NGS to identify molecular aberrations and generate an individualized treatment plan in this patient population. A randomized treatment study utilizing lessons learned from the conduct of this pilot study is currently underway.

PMID:
26063764
PMCID:
PMC5560131
DOI:
10.1158/1535-7163.MCT-15-0153
[Indexed for MEDLINE]
Free PMC Article

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