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

Research output: Contribution to journalArticle

300 Scopus citations

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 hadBMfrom 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.

Original languageEnglish (US)
Pages (from-to)895-902
Number of pages8
JournalJournal of Clinical Oncology
Volume31
Issue number7
DOIs
StatePublished - Mar 1 2013

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Welsh, J. W., Komaki, R., Amini, A., Munsell, M. F., Unger, W., Allen, P. K., Chang, J. Y., Wefel, J. S., McGovern, S. L., Garland, L. L., Chen, S. S., Holt, J., Liao, Z., Brown, P., Sulman, E., Heymach, J. V., Kim, E. S., & Stea, B. (2013). Phase II trial of erlotinib plus concurrent whole-brain radiation therapy for patients with brain metastases from non-small-cell lung cancer. Journal of Clinical Oncology, 31(7), 895-902. https://doi.org/10.1200/JCO.2011.40.1174