Phase II trial of erlotinib plus concurrent whole-brain radiation therapy for patients with brain metastases from non-small-cell lung cancer
James W Welsh, Ritsuko Komaki, Arya Amini, Mark F Munsell, Wyatt Unger, Pamela K Allen, Joe Y Chang, Jeffrey S Wefel, Susan L McGovern, Linda L Garland, Su S Chen, Jamie Holt, Zhongxing Liao, Paul Brown, Erik Sulman, John V Heymach, Edward S Kim, Baldassarre Stea, James W Welsh, Ritsuko Komaki, Arya Amini, Mark F Munsell, Wyatt Unger, Pamela K Allen, Joe Y Chang, Jeffrey S Wefel, Susan L McGovern, Linda L Garland, Su S Chen, Jamie Holt, Zhongxing Liao, Paul Brown, Erik Sulman, John V Heymach, Edward S Kim, Baldassarre Stea
Abstract
Purpose: Brain metastasis (BM) is a leading cause of death from non-small-cell lung cancer (NSCLC). Reasoning that activation of the epidermal growth factor receptor (EGFR) contributes to radiation resistance, we undertook a phase II trial of the EGFR inhibitor erlotinib with whole-brain radiation therapy (WBRT) in an attempt to extend survival time for patients with BM from NSCLC. Additional end points were radiologic response and safety.
Patients and methods: Eligible patients had BM from NSCLC, regardless of EGFR status. Erlotinib was given at 150 mg orally once per day for 1 week, then concurrently with WBRT (2.5 Gy per day 5 days per week, to 35 Gy), followed by maintenance. EGFR mutation status was tested by DNA sequencing at an accredited core facility.
Results: Forty patients were enrolled and completed erlotinib plus WBRT (median age, 59 years; median diagnosis-specific graded prognostic assessment score, 1.5). The overall response rate was 86% (n = 36). No increase in neurotoxicity was detected, and no patient experienced grade ≥ 4 toxicity, but three patients required dose reduction for grade 3 rash. At a median follow-up of 28.5 months (for living patients), median survival time was 11.8 months (95% CI, 7.4 to 19.1 months). Of 17 patients with known EGFR status, median survival time was 9.3 months for those with wild-type EGFR and 19.1 months for those with EGFR mutations.
Conclusion: Erlotinib was well tolerated in combination with WBRT, with a favorable objective response rate. The higher-than-expected rate of EGFR mutations in these unselected patients raises the possibility that EGFR-mutated tumors are prone to brain dissemination.
Trial registration: ClinicalTrials.gov NCT00871923.
Conflict of interest statement
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
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Source: PubMed