Yes: Both patients and science can benefit from genomic analysis of tumors.
Use of molecular profiling of gastrointestinal tumors is ready for prime time. My contention is that both patients and science can benefit from genomic analysis of tumors.
Genomic analysis is now feasible in clinical practice because next-generation sequencing panels have been made available to us now by the enormous drop in the cost. The current cost of about $5,000-$6,000 per test for a comprehensive genomic sequencing is well within the range of feasibility, and we expect it to become less expensive.
The technology is robust, reliable, and flexible. It allows for broad sequencing of the whole expressed panel or targeted sequencing in an area of interest. And data suggest that the technology has sensitivity for DNA alterations exceeding 95% (Nat. Biotechnol. 2013;31:1023-31).
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Dr. Peter J. O'Dwyer
We can find actionable mutations. Our group sequenced tumors from 101 patients with colorectal cancer and found that 42% could have an approved or investigational therapy that was directed by the assay. This frequency reassuringly mirrors that of larger databases, and actionable mutations are similarly common in other gastrointestinal malignancies.
We can’t really recommend who should be tested. Testing is an option, but it is not currently standard of care, it’s not validated yet to contribute to the overall benefit of patients. So it may be better to consider whom not to test: patients who don’t need a treatment option or who are too sick to receive the treatment, and possibly those who have tumors that rarely yield positive findings.
A key question is whether there is benefit to patients. Perhaps the main benefit is that genomic analysis may make them eligible for investigational therapies. Your patients with GI cancers may be candidates for enrollment in several ongoing trials, such as FOCUS4, MODUL, and Signature, and several forthcoming trials, such as MATCH and ASSIGN.
It is not yet clear whether patients derive benefit in terms of tumor response. Response is currently anecdotal; we really don’t have the denominators to quantify the level of benefit here. And off-label use of drugs can be hard to negotiate with both companies and insurance, which may affect applicability to individual patients.
Science can benefit from performing genomic analysis for several reasons. Such analysis tests whether knowing the genomic sequence can define useful therapies. We have good responses in uncommon diseases and in subsets of common diseases, but we need to know if defining the genomic aberrations can make us better at treating the diseases in question by virtue of the drugs and what we know of the pathways. Findings will also help us determine how this approach of genomic-informed therapy selection fits into the context of other high-priority therapeutic research in this field.
Dr. Peter J. O’Dwyer is director of the developmental therapeutics program, Abramson Cancer Center, and professor of medicine, University of Pennsylvania, Philadelphia. Dr. O’Dwyer disclosed that he owns stock in TetraLogic; has a consulting or advisory role with Genentech; receives research funding from Bristol-Myers Squibb, Pfizer, Novartis, Genentech, Mirati Therapeutics, Celgene, GlaxoSmithKline, and BBI; and provides expert testimony for Eli Lilly.