Erlotinib plus whole-brain radiotherapy improves survival in NSCLC patients with brain metastases.
Major finding: Erlotinib plus whole-brain radiotherapy improves survival in NSCLC patients with brain metastases.
Concept: EGFR-mutant tumors may be especially prone to brain dissemination.
Impact: Concurrent erlotinib and radiotherapy may benefit patients with EGFR-mutant metastatic tumors.
For the approximately 20% to 40% of patients with non–small cell lung cancer (NSCLC) who develop brain metastases, the median survival after whole-brain radiotherapy (WBRT) has historically been less than 6 months. Overexpression of EGF receptor (EGFR), which is mutated in 10% to 15% of patients with NSCLC, has been implicated in resistance to radiotherapy, and erlotinib, an EGFR inhibitor that may penetrate the blood–brain barrier, can sensitize cancer cells to radiation in vitro. Welsh and colleagues therefore evaluated the effect of concurrent erlotinib and WBRT on brain metastases arising from NSCLC in a prospective phase II study with endpoints of increased overall survival compared with historical controls, radiologic response, and safety. Patients were unselected for EGFR status, and because erlotinib was not yet standard first-line therapy for NSCLC during the patient enrollment period, previous treatments were limited to systemic chemotherapy or stereotactic radiosurgery. The combination of erlotinib and WBRT was well tolerated, and no grade 4 or 5 adverse effects were observed. The overall response rate was 86% in those assessed for radiologic central nervous system (CNS) response, with 31% of patients experiencing a complete CNS response. Overall survival after concurrent erlotinib and WBRT exceeded that of historical controls, with a median survival of 11.8 months. Of note, the median overall survival was 9.3 months in patients with EGFR–wild-type NSCLC and 19.1 months in patients with EGFR-mutant NSCLC. EGFR mutations were present in 53% of patients, a significantly higher rate than NSCLC in general, raising the possibility that EGFR mutation may be linked to brain dissemination. Although this was a small nonrandomized study and first-line erlotinib usage may lead to different outcomes, these findings suggest that concurrent erlotinib and WBRT may be a safe and effective treatment for brain metastases from NSCLC.