The American Society of Clinical Oncology (ASCO) has released a provisional clinical opinion (PCO) calling for patients with newly diagnosed advanced non-small cell lung cancer to be tested for an epidermal growth factor receptor (EGFR) mutation prior to initiating first-line therapy with an EGFR tyrosine kinase inhibitor (TKI). ASCO said the decision was made after 5 randomized, controlled trials demonstrated improved progression-free survival for patients with the EGFR mutation who were treated with gefinitinb (Iressa) or erlotinib (Tarceva). No study has linked targeting EGFR TKI therapy to patients with an activating EGFR mutation to improvement in overall survival.
The PCO notes that nearly 15% of patients with adenocarcinoma of the lung have an activating EGFR mutation, and testing is available at most academic medical centers and some community practices.
The panel looked at 5 trials that compared a standard platinum-based chemotherapy regimen with an EGFR TKI. The phase 3 IPASS (Iressa Pan-Asian Study) trial by Mok and associates reported median progression-free survival of 9.5 months for EGFR-positive patients receiving gefitinib compared with 6.3 months for EGFR-positive patients treated with chemotherapy. The use of gefitinib in patients who tested negative for the EGFR mutation was associated with significantly poorer progression-free survival than chemotherapy (1.5 months versus 5.5 months, respectively; P <.001), which also underscores why testing is important prior to using an EGFR TKI. Second- and third-line studies of erlotinib, which is more commonly available in the United States, suggested improved progression-free survival for EGFR-positive patients taking erlotinib.
The PCO notes that neither gefitinib or elrotinib have been approved by the US Food and Drug Administration (FDA) for first-line treatment of advanced non-small cell lung cancer. Nor has the FDA given clearance to any EGFR mutation test. The panel states that fluorescent in situ hybridization and immunohistochemistry testing for EGFR are not recommended as a basis for treatment decisions.
