The chorus of support is growing among oncology experts for routine genetic testing of tumors from patients with advanced non-small cell lung cancer (NSCLC) to determine whether these patients should receive a tyrosine kinase inhibitor (TKI) or chemotherapy as first-line treatment.
The American Society of Clinical Oncology (ASCO) said in a provisional clinical opinion this week that the results of 5 randomized phase III trials showed that positive mutations of the epidermal growth factor receptor (EGFR
) gene predict the clinical benefits of the targeting agents.
Patients who test positive for EGFR
mutations, which can lead to uncontrolled cell division, have higher response rates to the TKIs erlotinib (Tarceva) and gefitinib (Iressa). Those with negative tests for EGFR
mutations experience better responses with the standard chemotherapy combination of carboplatin and paclitaxel.
Earlier this year, the National Comprehensive Cancer Network similarly called for EGFR
testing of NSCLC patients with tumors of all histologies except squamous cell carcinoma.
testing helps us move toward the goal of tailoring cancer treatments for each patient,” Vicki Keedy, MD, a co-chair of the ASCO panel who is assistant professor of medicine at Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, said in a press release. “We’ve learned over the years that non-small cell lung cancer is really a collection of genetically distinct diseases. We want to treat patients with drugs that target the molecular drivers of their specific tumors, rather than using a one-size-fits-all approach.”
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Keedy also noted, however, that it is unclear whether or not this approach affects the overall survival of these patients.
The panel said its recommendation “applies mainly, but not exclusively” to NSCLC patients with adenocarcinoma histologies. Approximately 15% of patients with adenocarcinoma-type NSCLC carry EGFR
mutations; overall, NSCLC make up about 80% of the estimated 220,500 new cases of lung cancer diagnosed annually in the United States.
The ASCO panel said the major impetus for its recommendations was the Iressa Pan-Asian Study, which compared gefitinib with chemotherapy among patients who were either never-smokers or light smokers. Smaller studies examined erlotinib, which the panel said is similar to gefitinib.
In the United States, erlotinib is approved as second-line therapy while gefitinib has limited approval and is not readily available, the panel noted.
The panel identified a number of research priorities going forward, including a head-to-head comparison of erlotinib and gefitinib.
Reference:Keedy VL, Temin S, Somerfield MR, et al. American Society of Clinical Oncology provisional clinical opinion: epidermal growth factor receptor (EGFR) mutation testing for patients with advanced non-small cell lung cancer considering first-line EGFR tyrosine kinase inhibitor therapy [Published online ahead of print April 11, 2011]. J Clin Oncol. doi:10.1200/JCO.2010.31.8923