Zhenzhou Yang1,2, Yan Zhang3, Rongqing Li4, Abulimiti Yisikandaer5, Biyong Ren6, Jianguo Sun7, Jianjun Li8, Long Chen9, Ren Zhao10, Juying Zhang11, Xuefeng Xia12, Zhongxing Liao13, David P Carbone14. 1. Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. 2. Cancer Center, Research Institute of Surgery, Daping Hospital, Chongqing, China. 3. Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China. 4. Department of Radiation Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, China. 5. Department of Radiotherapy of the Chest and Abdomen, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China. 6. Institute for Cancer Prevention and Treatment, Chongqing Sanxia Central Hospital, Chongqing, China. 7. Department of Medical Oncology, Xinqiao Hospital, Chongqing, China. 8. Department of Oncology, Southwest Hospital, Chongqing, China. 9. Department of Radiation Oncology, Cancer Hospital, Guangxi Medical University, Nanning, China. 10. Department of Radiotherapy, General Hospital of Ningxia Medical University, Yinchuan, China. 11. Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China. 12. GenePlus-Beijing Institute, Peking University Medical Industrial Park, Zhongguancun Life Science Park, Beijing, China. 13. Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 14. Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Medical Center, Columbus, Ohio, USA.
Abstract
BACKGROUND: Erlotinib 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. METHODS: NSCLC 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). RESULTS: A 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. CONCLUSION: Concurrent 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: NCT01887795.
BACKGROUND: Erlotinib 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. METHODS: NSCLC 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). RESULTS: A 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. CONCLUSION: Concurrent 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: NCT01887795.
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