NEW YORK (Reuters Health) – For patients with advanced, untreated non-small-cell lung cancer, the American Society of Clinical Oncology recommends that the tumor be tested for genetic mutations in the epidermal growth factor receptor (EGFR), to see if first line treatment should be with an EGFR tyrosine kinase inhibitor or combination chemotherapy.

That ASCO “Provisional Clinical Opinion”, compiled by Dr. Vicki Leigh Keedy of Vanderbilt University Medical Center in Nashville, Tennessee and colleagues, is published in the Journal of Clinical Oncology online April 11.

The panel notes that in the US, some 15% of patients with adenocarcinoma of the lung harbor activating EGFR mutations. Such patients benefit from treatment with EGFR tyrosine kinase inhibitors (TKIs), namely, erlotinib or gefitinib. However, neither TKI has been approved for first-line therapy of lung cancer by the US Food and Drug Administration.

In forming their recommendations, the authors reviewed five phase III randomized controlled trials comparing progression-free survival or overall survival in patients with advanced non-small-cell lung cancer (NSCLC) lung cancer patients treated with TKIs or chemotherapy, with respect to tumor EGFR mutation status.

In the largest study, known as IPASS, the hazard ratio (HR) for progression or death with gefitinib versus carboplatin/paclitaxel as first-line therapy, was 0.48 for patients who tested positive for EGFR activating mutations and 2.85 for those without such mutations. However, a follow-up analysis showed no overall survival advantage with either treatment regardless of mutation status.

The panel found that the results of the four other studies support the findings of the IPASS analysis — that is, prolonged progression-free survival and higher response rates for patients who tested positive for EGFR activating mutations and who received an EGFR TKI.

While noting some difficulties with testing tumor samples for EGFR mutations, the authors conclude: “On the basis of the results of five phase III RCTs, patients with advanced NSCLC of the lung who are being considered for first-line therapy with an EGFR TKI (patients who have not previously received chemotherapy or an EGFR TKI) should have their tumor tested for EGFR mutations to determine whether an EGFR TKI or chemotherapy is the appropriate first-line therapy.”

Reference:

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


J Clin Oncol 2011;29.