Epidermal growth factor receptor tyrosine kinase inhibitors as a first-line therapy for never-smokers with adenocarcinoma of the lung having asymptomatic synchronous brain metastasis

Abstract

Considering whole-brain radiotherapy (WBRT) for asymptomatic brain metastases can reduce performance status and delay systemic treatment, primary chemotherapy can be a feasible alternative treatment. Good and rapid response to epidermal growth factor tyrosine kinase inhibitor (EGFR TKI) treatment makes this an attractive option for never-smokers with adenocarcinoma of the lung. Between January 2005 and August 2007, 23 Korean never-smoking patients with adenocarcinoma of the lung who had synchronous asymptomatic brain metastasis were consecutively treated with EGFR TKI therapy, either gefitinib 250 mg or erlotinib 150 mg once daily, as first-line treatment after giving informed consent, until disease progression, unacceptable toxicity or patient's refusal. They have not received either any prior chemotherapy or any radiotherapy including stereotactic radiosurgery. Objective tumor responses were assessed 1 month after treatment and then every 2 months or when clinically indicated. Out of the 23 patients treated, 16 achieved a PR and 3 experienced stable disease (SD) while 4 experienced progressive disease (PD), resulting in a response rate of 69.6% and a disease control rate of 82.6%. Intracranial tumor responses were observed in 17 patients (73.9%). After a median follow-up of 21.8 months, the median progression-free and overall survival (OS) time was 7.1 and 18.8 months, respectively. Eleven patients received WBRT with a median time-to-local-treatment for intracranial tumors of 19.3 months. In conclusion, EGFR TKI treatment showed promising antitumor activity against both intracranial and extracranial tumors in chemotherapy-naïve never-smokers with adenocarcinoma of the lung. Therefore, these agents should be considered as the treatment of choice in this clinical setting.

Introduction

The primary treatment for brain metastases in patients with non-small cell lung cancer (NSCLC) has traditionally consisted of whole-brain radiotherapy (WBRT), surgery, or radiosurgery, while systemic chemotherapy has been thought to play a limited role because of the belief that the brain is a pharmacologic sanctuary site [1], [2]. However, systemic chemotherapy prior to WBRT might be considered a more feasible and appropriate option for chemotherapy-naïve patients with asymptomatic synchronous brain metastases, specifically with regards to survival outcomes, toxicity profiles, and quality of life. Furthermore, previous studies have determined that WBRT is not always necessary [3], [4]. Epidermal growth factor (EGFR) tyrosine kinase inhibitors (TKI's) result in high response rates and mild toxicity in never-smokers with adenocarcinoma [5], [6]. Gefitinib has reportedly been active on brain metastases, while incidence of disease recurrence in the brain after response to gefitinib has been also reported [7], [8], [9]. Therefore, we investigated retrospectively the efficacy of EGFR TKI treatment for asymptomatic synchronous brain metastases in chemotherapy-naïve never-smokers with adenocarcinoma of the lung.