Faculty Collaboration Database

On the Road to Precision Cancer Medicine: Analysis of Genomic Biomarker Actionability in 439 Patients. Mol Cancer Ther 2015 Jun;14(6):1488-94

Date

04/09/2015

Pubmed ID

25852059

DOI

10.1158/1535-7163.MCT-14-1061

Scopus ID

2-s2.0-84937990975 (requires institutional sign-in at Scopus site)   75 Citations

Abstract

Despite the increased use of molecular diagnostics, the extent to which patients who have these tests harbor potentially actionable aberrations is unclear. We retrospectively reviewed 439 patients with diverse cancers, for whom next-generation sequencing (mostly 236-gene panel) had been performed. Data pertaining to the molecular alterations identified, as well as associated treatment suggestions (on- or off-label, or experimental), were extracted from molecular diagnostic reports. Most patients (420/439; 96%) had at least one molecular alteration: 1,813 alterations (in 207 distinct genes) were identified [the majority being mutations (62%) or amplifications (29%)]. The three most common gene abnormalities were TP53 (44%), KRAS (16%), and PIK3CA (12%). The median number of alterations per patient was 3 (range, 0-16). Nineteen patients (4%) had no alterations; 48 patients (11%) had only one alteration; and 372 patients had two or more abnormalities (85%). The median number of potentially actionable anomalies per patient was 2 (range, 0-8). Most patients (393/439; 90%) had at least one potentially actionable alteration, and in all these cases the aberration could at least be targeted by an experimental drug in a clinical trial. A total of 307 patients (70%) had an alteration that was actionable with an approved drug, but in only 89 patients (20%) was the drug approved for their disease (on-label). Next-generation sequencing identified theoretically actionable aberrations in 90% of our patients. Many of the drugs are, however, experimental or would require off-label use. Strategies to address drug access for patients harboring potentially actionable mutations are needed.

Author List

Schwaederle M, Daniels GA, Piccioni DE, Fanta PT, Schwab RB, Shimabukuro KA, Parker BA, Kurzrock R

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Biomarkers, Tumor
Female
Gene Amplification
Gene Frequency
Genetic Predisposition to Disease
Genomics
High-Throughput Nucleotide Sequencing
Humans
Male
Middle Aged
Mutation
Neoplasms
Precision Medicine
Retrospective Studies