“If you build it, they will come,” the saying goes, but has that been the case with genetic/genomic testing in patients with newly diagnosed non-small cell lung cancer (NSCLC)? After all, research has shown that about 40% of patients with NSCLC have one of these molecular alterations in their tumor, and using these tests can help sort out those who have KRAS-mutated disease, versus epidermal growth factor receptor (EGFR) mutations, versus ALK, ROS1, or RET translocations, guiding patients to the most effective targeted therapy.
A recent international survey of oncologists revealed that while the use of genetic/genomic is on the rise, many clinicians are either bypassing testing altogether, or if the patient did undergo testing, the results were not used to make treatment decisions.
For instance, EGFR mutations are currently the most common genomically classified subgroup of NSCLC. These mutations tend to be more prevalent in tumors with adenocarcinoma histology, in patients who have never smoked tobacco, in patients of East Asian race, and women. Results of genetic/genomic testing can then set patients up for treatment with agents such as gefitinib (Iressa) and erlotinib (Tarceva).
Guidelines established by specialty groups, including the College of American Pathologists and the International Association for the Study of Lung Cancer, recommend testing for EGFR mutations (along with testing for ALK mutations) in patients with advanced-stage disease. Whether early-stage patients should undergo the same is uncertain.
“The question of whether or not to test a diagnostic specimen in early-stage disease is a local decision that must be made in conjunction with each institution’s oncology care team, as insufficient published evidence supports a universal recommendation,” according to 2013 guidelines from the groups mentioned above. “The benefits of testing all early-stage disease patients must be balanced against the cost of performing testing that may not be used to select therapy for the patients who never have relapse.”
But genetic screening in early NSCLC isn’t out of the question, wrote Jean-Charles Soria, MD, PhD, of Gustave Roussy Cancer Center in Villejuif, France, in an email to MedPage Today. He pointed out that there is a debate over the risk of relapse in stage I-II cancer, but even if that risk is over a 5-year period, it “reaches 50%, so I also believe it could help.”
For example, early testing can rule out if a patient is simply ineligible for treatment with gefitinib, an EGFR tyrosine kinase inhibitor (TKI). Nowak cited a 2012 study that she and Soria co-authored that found that EGFR testing avoided a median of 8 weeks of administration of gefitinib for EGFR-negative patients.
An added benefit to testing? The potential for a significant reduction in treatment costs. “In France in 2010, about 15,000 of the 16,834 patients with lung cancer who benefited from EGFR screening were EGFR-mutation negative and thus were ineligible for TKI-EGFR treatment,” Nowak stated.
“As 8 weeks of gefitinib treatment costs €4,600 per patient in France [about $5,000], this would mean overall savings of €69 million [about $74 million]. According to the numbers of EGFR tests performed in 2011, the spared costs should be even greater,” she added.
Seven years ago, INCa, along with the French Ministry of Health, launched a campaign to implement molecular testing for all cancer patients across the French national healthcare system. The network is made up of 28 regional molecular genetic centers that perform tests for free for all patients in their regions.
Back to the survey results, which revealed that one of the impediments to implementing genetic testing in newly diagnosed patients may be the wait for the results – the turnaround time for test findings can range from 1 to 2 weeks. About a quarter of U.S.-based survey respondents stating that was too long.
In general, lung cancer takes some time to develop before a diagnosis is made; a few extra days of waiting for test results that can have a major impact on treatment course and patient outcomes shouldn’t be that onerous, noted survey leader James Spicer, PhD, MBBS, of King’s College London.
“Personally — and I think this is a fairly common viewpoint — turnaround within 1 week — 5 working days — would definitely be acceptable; 2 weeks or more becomes a problem,” he said.
While Spicer told MedPage Today that he wasn’t surprised by the survey results, his group also did not find any evidence that clinicians were skeptical about EGFR testing overall. Instead, it may be a matter of continual education to emphasize the benefits of genetic testing in NSCLC patients across the board.
“We should be aiming for every suitable NSCLC patient to be tested, and every patient receiving an appropriate treatment for their type of lung cancer,” Spicer said in a written statement about the survey results. He added that “there is still work to be done in emphasizing the importance of obtaining EGFR test results prior to the initiation of treatment, and using this vital information to select optimum therapy.”