DNA-Mutation Inventory to Refine and Enhance Cancer Treatment (DIRECT): a catalog of clinically relevant cancer mutations to enable genome-directed anticancer therapy - PubMed (original) (raw)

Meta-Analysis

DNA-Mutation Inventory to Refine and Enhance Cancer Treatment (DIRECT): a catalog of clinically relevant cancer mutations to enable genome-directed anticancer therapy

Paul Yeh et al. Clin Cancer Res. 2013.

Abstract

Purpose: Tumor gene mutation status is becoming increasingly important in the treatment of patients with cancer. A comprehensive catalog of tumor gene-response outcomes from individual patients is needed, especially for actionable mutations and rare variants. We created a proof-of-principle database [DNA-mutation Inventory to Refine and Enhance Cancer Treatment (DIRECT)], starting with lung cancer-associated EGF receptor (EGFR) mutations, to provide a resource for clinicians to prioritize treatment decisions based on a patient's tumor mutations at the point of care.

Methods: A systematic search of literature published between June 2005 and May 2011 was conducted through PubMed to identify patient-level, mutation-drug response in patients with non-small cell lung cancer (NSCLC) with EGFR mutant tumors. Minimum inclusion criteria included patient's EGFR mutation, corresponding treatment, and an associated radiographic outcome.

Results: A total of 1,021 patients with 1,070 separate EGFR tyrosine kinase inhibitor therapy responses from 116 different publications were included. About 188 unique EGFR mutations occurring in 207 different combinations were identified: 149 different mutation combinations were associated with disease control and 42 were associated with disease progression. Four secondary mutations, in 16 different combinations, were associated with acquired resistance.

Conclusions: As tumor sequencing becomes more common in oncology, this comprehensive electronic catalog can enable genome-directed anticancer therapy. DIRECT will eventually encompass all tumor mutations associated with clinical outcomes on targeted therapies. Users can make specific queries at http://www.mycancergenome.org/about/direct to obtain clinically relevant data associated with various mutations.

©2013 AACR.

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Conflict of interest statement

Disclosure of Potential Conflicts of Interest

W. Pao has received consulting fees from MolecularMD, AstraZeneca, Bristol-Myers Squibb, Symphony Evolution, and Clovis Oncology and research funding for other projects from Enzon, Xcovery, AstraZeneca, and Symphogen. W. Pao is part of a patent regarding EGFRT790M mutation testing that was licensed by Memorial Sloan-Kettering Cancer Center to Molecular MD. L. Horn is a consultant/advisory board member of Astellas, BI, Genentech. No potential conflicts of interest were disclosed by the other authors.

Figures

Figure 1

Figure 1. Schematic flowchart of DIRECT database and patient cohort formation. Number of unique patients does not match the number of therapy-response entries as one patient may have been treated with EGFR TKIs in different lines of treatment and thus have multiple associated therapy-response entries

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References

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