Whole-brain radiotherapy with and without concurrent erlotinib in NSCLC with brain metastases: a multicenter,open-label,randomized, controlled phase III trial |
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Authors: | Zhenzhou Yang Yan Zhang Rongqing Li Abulimiti Yisikandaer Biyong Ren Jianguo Sun Jianjun Li Long Chen Ren Zhao Juying Zhang Xuefeng Xia Zhongxing Liao David P Carbone |
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Abstract: | BackgroundErlotinib combined with whole-brain radiotherapy (WBRT) demonstrated a favorable objective response rate in a phase II single-arm trial of non–small cell lung cancer (NSCLC) patients with brain metastases. We assessed whether concurrent erlotinib with WBRT is safe and benefits patients in a phase III, randomized trial.MethodsNSCLC patients with two or more brain metastases were enrolled and randomly assigned (1:1) to WBRT (n = 115) or WBRT combined with erlotinib arms (n = 109). The primary endpoint was intracranial progression-free survival (iPFS) and cognitive function (CF) was assessed by the Mini-Mental State Examination (MMSE).ResultsA total of 224 patients from 10 centers across China were randomized to treatments. Median follow-up was 11.2 months. Median iPFS for WBRT concurrent erlotinib was 11.2 months vs 9.2 months for WBRT-alone (P = .601). Median PFS and overall survival (OS) of combination group were 5.3 vs 4.0 months (P = .825) and 12.9 vs 10.0 months (P = .545), respectively, compared with WBRT-alone. In EGFR-mutant patients, iPFS (14.6 vs 12.8 months; P = .164), PFS (8.8 vs 6.4 months; P = .702), and OS (17.5 vs 16.9 months; P = .221) were not significantly improved in combination group over WBRT-alone. Moreover, there were no significant differences in patients experiencing MMSE score change between the treatments.ConclusionConcurrent erlotinib with WBRT didn’t improve iPFS and excessive CF detriment either in the intent-to-treat (ITT) population or in EGFR-mutant patients compared with WBRT-alone, suggesting that while safe for patients already taking the drug, there is no justification for adding concurrent EGFR-TKI with WBRT for the treatment of brain metastases. Trial registration: Clinical trials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT01887795","term_id":"NCT01887795"}}NCT01887795 |
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Keywords: | brain metastases, epidermal growth factor receptor, erlotinib, non– small cell lung cancer, whole-brain radiation therapy |
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