Phase II trial of erlotinib plus concurrent whole-brain radiation therapy for patients with brain metastases from non-small-cell lung cancer
Open accessAbstract
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.
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That phase II study established the feasibility and tolerability of erlotinib with WBRT for patients with EGFR-mutant NSCLC who have numerous or symptomatic brain metastases and require urgent systemic therapy at the time of WBRT.
“The study established the feasibility and tolerability of this option for patients with EGFR-mutant NSCLC who have numerous or symptomatic brain metastases and require simultaneous urgent initiation of systemic therapy at the time of WBRT.”
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- Authors
- 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.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2013-03-01
- Volume
- 31
- Issue
- 7
- Pages
- 895-902
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- PMC
- PMC3577951
- OpenAlex
- W2114464493
- Cited by
- 395
- References
- 30
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 10 · 2023: 11 · 2022: 13 · 2021: 15 · 2020: 24 · 2019: 31 · 2018: 42 · 2017: 48 · 2016: 64 · 2015: 48 · 2014: 42 · 2013: 31 · 2012: 4
- FWCI
- 50.23
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Clinical Oncology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (U10-CA-21661, U10CA021661, P30CA016672)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Brain Metastases and Treatment
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Keywords
- erlotinib, whole brain radiotherapy, brain metastases, non-small cell lung cancer, EGFR inhibitors, epidermal growth factor receptor, EGFR mutation, radioresistance (biology), combination therapy, survival, neurotoxicity
- MeSH terms
- Erlotinib Hydrochloride, Adult, Aged, Antineoplastic Agents, Brain Neoplasms, Carcinoma, Non-Small-Cell Lung, Drug Eruptions, Drug Administration Schedule, Female, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Prospective Studies, Quinazolines, Cranial Irradiation, Treatment Outcome, Genetic Predisposition to Disease, Kaplan-Meier Estimate, Chemoradiotherapy, ErbB Receptors
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