Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors as a First-Line Therapy for Never-Smokers with Adenocarcinoma of the Lung and Asymptomatic Synchronous Brain Metastasis

Abstract

BackgroundAs routine initial evaluation with improved neuroimaging technique increases incidence of brain metastases in advanced/metastatic non—small-cell lung cancer, we face a dilemma to choose initial treatment for patients with asymptomatic brain metastasis. On the other hand, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib reportedly have high response rates for patients who have never smoked and have adenocarcinoma histology. Based on those findings, we studied the efficacy of the EGFR TKIs as a first-line therapy for never-smokers with metastatic adenocarcinoma of the lung and asymptomatic synchronous brain metastases. Patients and MethodsThe eligible patient should be a never-smoker with adenocarcinoma of the lung and asymptomatic synchronous brain metastases. Additional inclusion criteria are as follows: Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0–3, adequate organ function, and measurable disease in both extracranial and intracranial sites. Neither previous chemotherapy nor radiation therapy, including stereotactic radiosurgery, was allowed. Treatment consisted of gefitinib 250 mg or erlotinib 150 mg orally given once daily until disease progression, unacceptable toxicity, or patient's refusal. Objective tumor responses were assessed every 2 months or clinically indicated. ResultsBetween January 2005 and August 2007, all 23 patients (median age, 60 years; male/female, 1/22; ECOG PS of 0–1/2–3, 11/12) were enrolled. Among them, 12 patients had no extrathoracic metastasis except brain. There were 15 partial responses (65.2%; 95% CI, 44.8%–81.3%), 3 stable diseases (13.0%), and 5 progressive diseases (21.7%), giving a disease control rate of 79.3%. With a median follow-up of 9 months, progression-free and overall survival was 6.4 months and 18.6 months, respectively. Among 17 patients showing progressive disease, 9 (39.1%) had to receive whole-brain radiation therapy because of the development of neurologic symptoms or signs. ConclusionsEGFR TKIs showed promising response rate as a first-line therapy for never-smokers with adenocarcinoma of the lung and asymptomatic synchronous brain metastases in both intracranial and extracranial sites, suggesting that these agents can be a treatment of choice in this clinical setting.