ASCO Recommends EGFR Testing for NSCLC, But for Which Patients?

Nick Mulcahy

April 28, 2011

April 28, 2011 — Epidermal growth-factor receptor (EGFR) mutation testing is now recommended by the American Society of Clinical Oncology (ASCO) for patients with advanced nonsmall-cell lung cancer (NSCLC) who are "considering" first-line therapy with the EGFR tyrosine kinase inhibitors (TKIs) erlotinib (Tarceva) and gefitinib (Iressa).

TKIs have been shown to improve response and progression-free survival in patients with EGFR-mutated NSCLC who received these targeted therapies in first-line treatment, according to an ASCO panel of experts who authored the new provisional clinical opinion published online April 11 in the Journal of Clinical Oncology.

The panel was headed by Vicki Leigh Keedy, MD, from Vanderbilt University Medical Center in Nashville, Tennessee.

"Patients with EGFR-mutated NSCLC have a significantly higher rate of partial responses to the EGFR TKIs gefitinib and erlotinib," writes the panel.

Despite the new recommendation, the panel admits that "there is no evidence of an overall survival benefit from selecting treatment" on the basis of EGFR status.

Also, neither drug is currently approved for the first-line therapy of lung cancer by the US Food and Drug Administration (FDA).

Patient Selection — Difference of Opinion on Panel

The ASCO opinion does not state exactly which patients should consider and receive the mutation testing.

However, Dr. Keedy provided some insight to Medscape Medical News.

"Patients typically considered for first-line EGFR TKI therapy are those who are never smokers or former light smokers," she explained.

"Some physicians will consider first-line EGFR TKI therapy for elderly patients or patients with poor performance status, regardless of smoking status," she added. Dr. Keedy also noted that the drugs should only be offered in these latter circumstances to those patients who have EGFR mutations.

But another member of the ASCO panel thinks differently.

"Any patient could consider being tested, regardless of histology. Although rare, even squamous carcinomas may have EGFR mutations that render the tumor sensitive to a TKI," said Giuseppe Giaccone, MD, from Stanford University in Palo Alto, California, in an email to Medscape Medical News.

Another lung cancer expert, who was not part of the ASCO panel, said that not every NSCLC patient needs EGFR testing.

Heavy smokers and patients with squamous cell carcinomas are very unlikely to have the EGFR mutation, H. Jack West, MD, from the Swedish Cancer Institute in Seattle, Washington, told Medscape Medical News last year.

"The most suitable candidates for testing are never smokers or those with a remote smoking history with an adenocarcinoma," he said.

But Dr. West also said that he offers an EGFR TKI to all NSCLC patients who progress, even those who do not test positive for the EGFR mutation.

"Being EGFR wildtype, however, does not mean that someone will get no benefit from an EGFR TKI," he wrote in one entry of his Medscape blog, Blowing Smoke.

ASCO Joins NCCN

In issuing its provisional clinical opinion, ASCO joins the National Comprehensive Cancer Network (NCCN) in endorsing EGFR mutation testing for lung cancer patients who are candidates for first-line TKI therapy.

The NCCN also recommends erlotinib in the United States as first-line therapy for patients who have an EGFR mutation and who have advanced, recurrent, or metastatic nonsquamous cell NSCLC.

The new ASCO opinion is based on the results of 5 randomized clinical trials, the largest and most important of which is the Iressa Pan-Asia Study (IPASS) trial. "The study demonstrated that gefitinib is superior to carboplatin/paclitaxel as an initial treatment for adenocarcinoma of the lung among nonsmokers or former light smokers in East Asia, based on [progression-free survival] findings," explains the ASCO panel.

In its review, the panel acknowledged that erlotinib, which is approved by the FDA as second-line therapy, is very similar to gefitinib, which is not readily available in the United States.

The new recommendation comes at a time when EGFR testing is still not widespread in the United States, suggest the ASCO authors.

"Such testing is currently available, both at academic medical centers and at some community medical centers," they write.

Recently, at the NCCN annual meeting, another expert suggested that the testing is not routine in the mid-Atlantic region.

David Ettinger, MD, from the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, Maryland, told the NCCN audience that he routinely sees NSCLC patients referred from the "5-state area," who have not received molecular testing, including that for EGFR mutation.

EGFR testing has a number of barriers keeping it from wider use, said Dr. West last year. "There are a limited number of labs that perform the test, and it can take 3 to 4 weeks to get results," Dr. West said, adding that most patients with lung cancer and their clinicians are "uneasy" about delaying the start of therapy for that long.

Also, initial lung biopsies often do not yield sufficient tissue for testing, necessitating another biopsy, he said.

ASCO panel members reporting financial relationships include Heather A. Wakelee, MD, from Stanford Cancer Center, Stanford University, California, who reports being a consultant/advisor to Genentech and receiving research funding from AstraZeneca and Genentech; and Daniel T. Milton, MD, from Hematology/Oncology of Indiana, Indianapolis, who reports receiving research funding from Genentech.

J Clin Oncol. Published online April 11, 2011. Full text

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