Open AccessEnabling a Genetically Informed Approach to Cancer Medicine: A Retrospective Evaluation of the Impact of Comprehensive Tumor Profiling Using a Targeted Next‐Generation Sequencing Panel
Author(s) -
Johnson Douglas B.,
Dahlman Kimberly H.,
Knol Jared,
Gilbert Jill,
Puzanov Igor,
MeansPowell Julie,
Balko Justin M.,
Lovly Christine M.,
Murphy Barbara A.,
Goff Laura W.,
Abramson Vandana G.,
Crispens Marta A.,
Mayer Ingrid A.,
Berlin Jordan D.,
Horn Leora,
Keedy Vicki L.,
Reddy Nishitha M.,
Arteaga Carlos L.,
Sosman Jeffrey A.,
Pao William
Publication year - 2014
Publication title -
the oncologist
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.176
H-Index - 164
eISSN - 1549-490X
pISSN - 1083-7159
DOI - 10.1634/theoncologist.2014-0011
Subject(s) - medicine , targeted therapy , oncology , clinical trial , bioinformatics , cancer , precision medicine , pathology , biology
Background. Oncogenic genetic alterations “drive” neoplastic cell proliferation. Small molecule inhibitors and antibodies are being developed that target an increasing number of these altered gene products. Next‐generation sequencing (NGS) is a powerful tool to identify tumor‐specific genetic changes. To determine the clinical impact of extensive genetic analysis, we reviewed our experience using a targeted NGS platform (FoundationOne) in advanced cancer patients. Patients and Methods. We retrospectively assessed demographics, NGS results, and therapies received for patients undergoing targeted NGS (exonic sequencing of 236 genes and selective intronic sequencing from 19 genes) between April 2012 and August 2013. Coprimary endpoints were the percentage of patients with targeted therapy options uncovered by mutational profiling and the percentage who received genotype‐directed therapy. Results. Samples from 103 patients were tested, most frequently breast carcinoma (26%), head and neck cancers (23%), and melanoma (10%). Most patients (83%) were found to harbor potentially actionable genetic alterations, involving cell‐cycle regulation (44%), phosphatidylinositol 3‐kinase‐AKT (31%), and mitogen‐activated protein kinase (19%) pathways. With median follow‐up of 4.1 months, 21% received genotype‐directed treatments, most in clinical trials (61%), leading to significant benefit in several cases. The most common reasons for not receiving genotype‐directed therapy were selection of standard therapy (35%) and clinical deterioration (13%). Conclusion. Mutational profiling using a targeted NGS panel identified potentially actionable alterations in a majority of advanced cancer patients. The assay identified additional therapeutic options and facilitated clinical trial enrollment. As time progresses, NGS results will be used to guide therapy in an increasing proportion of patients.