Journal Article

Comprehensive genomic profiling in routine clinical practice leads to a low rate of benefit from genotype-directed therapy

Arnold, Susanne M., Mathew, Aju, Hilal, Talal, Nakazawa, Mary, Anthony, Lowell B., Villano, John L., Hodskins, Jacob, Wagner, Lars, DeSimone, Philip, Hosein, Peter J., Goel, Guarav

2017

Overview

Background Describe a single-center real-world experience with comprehensive genomic profiling (CGP) to identify genotype directed therapy (GDT) options for patients with malignancies refractory to standard treatment options. Methods Patients who had CGP by a CLIA-certified laboratory between November 2012 and December 2015 were included. The medical records were analyzed retrospectively after Institutional Review Board (IRB) approval. The treating oncologist made the decision to obtain the assay to provide potential therapeutic options. The objectives of this study were to determine the proportion of patients who benefited from GDT, and to identify barriers to receiving GDT. Results A total of 125 pediatric and adult patients with a histologically confirmed diagnosis of malignancy were included. Among these, 106 samples were from adult patients, and 19 samples were from pediatric patients. The median age was 54 years for adults. The majority had stage IV malignancy (53%) and were pretreated with 2–3 lines of therapy (45%). The median age was 8 years for pediatric patients. The majority had brain tumors (47%) and had received none or 1 line of therapy (58%) when the profiling was requested. A total of 111 (92%) patients had genomic alterations and were candidates for GDT either via on/off-label use or a clinical trial (phase 1 through 3). Fifteen patients (12%) received GDT based on these results including two patients who were referred for genomically matched phase 1 clinical trials. Three patients (2%) derived benefit from their GDT that ranged from 2 to 6 months of stable disease. Conclusions CGP revealed potential treatment options in the majority of patients profiled. However, multiple barriers to therapy were identified, and only a small minority of the patients derived benefit from GDT.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adolescent / Adult / Adults / Age / Aged / Aged, 80 and over / Analysis / Biomedical and Life Sciences / Biomedicine / Brain cancer / Brain tumors / Breast cancer / Cancer Research / Cancer therapeutics / Cancer therapies / Care and treatment / Child / Child health / Child, Preschool / Clinical medicine / Clinical trials / Clinical Trials as Topic / Epidermal growth factor / Female / Genetic aspects / Genetics / Genomics / Genomics - methods / genomics and epigenetics / Genotype / Genotype-directed therapy / Health aspects / Health Promotion and Disease Prevention / Humans / Lung cancer / Male / Malignancy / Medical records / Medicine / Medicine/Public Health / Middle Aged / Mutation / Neoplasms - genetics / Oncology / Patients / Pediatrics / Profiling / Research Article / Retrospective Studies / Surgical Oncology / Therapeutic applications / Therapeutics / Tumors / Young Adult