Broad Genetic Testing for Advanced Lung Cancer May Not Improve Survival

August 08, 2018
Carolyn Presley

COLUMBUS, Ohio – Testing for dozens of genetic mutations in tumors of patients with a common form of advanced lung cancer does not appear to improve survival compared to routine genetic testing, according to a new research co-authored by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James).

Broad-based genomic sequencing (BGS) evaluates numerous genes to identify mutations in tumors of patients with advanced non-small cell lung cancer. If a mutation is found and a drug exists to target the mutation, BGS can help clinicians personalize and treat the disease. However, questions remain about how broad-based testing, which can be costly, compares to more routine testing that focuses on one or two established, treatable genetic mutations.

Carolyn Presley, MD, a medical oncologist and assistant professor at the OSUCCC – James, served as first author of the new study, published in the medical journal JAMA. She conducted the research while at Yale University in collaboration with colleagues there and at Flatiron Health.

For this study, the team analyzed more than 5,000 patients with advanced non-small cell lung cancer that were treated in a community oncology clinic. The researchers identified patients who received either BGS testing or routine testing for two specific genetic alterations, EGFR or ALK. They determined how frequently the BGS testing identified specific mutations that guided the choice of therapy and also compared overall survival rates for the patients receiving BGS with those receiving routine testing.

The research team found that among patients who received broad-based testing, very few also received a targeted treatment as a result.

Compared to patients who received routine tests, the BGS group did not have improved survival in the short or long term.

Authors note that patients who had this broad-based sequencing were no more likely to live longer than patients who did not have the test. This suggests that, with the current selection of targeted drugs that we have at our disposal, testing for dozens or hundreds of mutations as part of regular community practice may not be helping people to live longer. This could be due to limited targeted therapies at the time period the study was conducted, lack of clinical trial access, cost of new cancer drugs or insurance denials of off-label drug use.

"Our ability to sequence has outpaced our ability to get targeted therapies to patients at the right time,” says Presley. "We need to be able to track genetic testing results better between clinicians. We need more trials for novel cancer agents, and we need to make cancer drugs affordable for our patients."

The study results call into question the use of broad-based testing in routine care. While the tests are covered by Medicare, the costs of such testing can run thousands of dollars. Even when mutations are identified, there may not be an approved drug available to target them, the researchers said.

Broad-based testing has an important role in research but may not currently offer a survival benefit more generally. “This is an example of how enthusiasm for a test or procedure leapfrogs ahead of evidence,” said Cary Gross, MD, senior author of the study and professor of medicine at Yale University. “To ensure that new discoveries are able to fulfill their promise, our results suggest further evidence is needed to inform the care of patients with a variety of specific genetic alterations in their tumors before widely disseminating these new paradigms into clinical practice.”

Other study authors from the Yale team include Daiwei Tang, Pamela R. Soulos, Anne C. Chiang, Janina A. Longtine, Kerin B. Adelson, Roy S. Herbst and Weiwei Zhu.

The work for this project was funded in part by grants from the Veterans Affairs/Robert Wood Johnson Clinical Scholars Program and the Yale Lung SPORE Career Development Award. Author affiliations and disclosures are detailed in the paper published in JAMA.

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YALE MEDIA CONTACT:

Karen N. Peart, 203-432-1326 or karen.peart@yale.edu

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