Experience with precision genomics and tumor board, indicates frequent target identification, but barriers to delivery
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Alan H. Bryce1,2,3,*, Jan B. Egan3,*, Mitesh J. Borad1,2,3, A. Keith Stewart1,2,3, Grzegorz S. Nowakowski3,4, Asher Chanan-Khan3,5, Mrinal M. Patnaik3,4, Stephen M. Ansell3,4, Michaela S. Banck3,6, Steven I. Robinson3,6, Aaron S. Mansfield3,6, Eric W. Klee3,7, Gavin R. Oliver3,7, Jennifer B. McCormick7, Norine E. Huneke3, Colleen M. Tagtow3, Robert B. Jenkins8, Kandelaria M. Rumilla8, Sarah E. Kerr9, Jean-Pierre A. Kocher3,7, Scott A. Beck3, Martin E. Fernandez-Zapico10, Gianrico Farrugia3,11, Konstantinos N. Lazaridis3,11, Robert R. McWilliams3,6,12
1Hematology/Oncology, Mayo Clinic, Phoenix, AZ, U.S.A
2Mayo Clinic Cancer Center, Phoenix, AZ, U.S.A
3Center for Individualized Medicine, Mayo Clinic, Rochester, MN, U.S.A
4Hematology, Mayo Clinic, Rochester, MN, U.S.A
5Hematology/Oncology, Mayo Clinic, Jacksonville, FL, U.S.A
6Medical Oncology, Mayo Clinic, Rochester, MN, U.S.A
7Health Sciences Research, Mayo Clinic, Rochester, MN, U.S.A
8Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, U.S.A
9Anatomic Pathology, Mayo Clinic, Rochester, MN, U.S.A
10Schulze Center for Novel Therapeutics, Division of Oncology Research, Medical Oncology, Mayo Clinic, Rochester, MN, U.S.A
11Gastroenterology, Mayo Clinic, Rochester, MN, U.S.A
12Mayo Clinic Cancer Center, Rochester, MN, U.S.A
*These authors contributed equally to this work
Robert R. McWilliams, email: [email protected]
Keywords: precision medicine, cancer genomics, targeted therapeutics, genomic tumor board
Received: November 09, 2016 Accepted: February 15, 2017 Published: March 09, 2017
Background: The ability to analyze the genomics of malignancies has opened up new possibilities for off-label targeted therapy in cancers that are refractory to standard therapy. At Mayo Clinic these efforts are organized through the Center for Individualized Medicine (CIM).
Results: Prior to GTB, datasets were analyzed and integrated by a team of bioinformaticians and cancer biologists. Therapeutically actionable mutations were identified in 65% (92/141) of the patients tested with 32% (29/92) receiving genomically targeted therapy with FDA approved drugs or in an independent clinical trial with 45% (13/29) responding. Standard of care (SOC) options were continued by 15% (14/92) of patients tested before exhausting SOC options, with 71% (10/14) responding to treatment. Over 35% (34/92) of patients with actionable targets were not treated with 65% (22/34) choosing comfort measures or passing away.
Materials and Methods: Patients (N = 165) were referred to the CIM Clinic between October 2012 and December 2015. All patients received clinical genomic panel testing with selected subsets receiving array comparative genomic hybridization and clinical whole exome sequencing to complement and validate panel findings. A genomic tumor board (GTB) reviewed results and, when possible, developed treatment recommendations.
Conclusions: Treatment decisions driven by tumor genomic analysis can lead to significant clinical benefit in a minority of patients. The success of genomically driven therapy depends both on access to drugs and robustness of bioinformatics analysis. While novel clinical trial designs are increasing the utility of genomic testing, robust data sharing of outcomes is needed to optimize clinical benefit for all patients.
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