title: Gefitinib and erlotinib for non-small cell lung cancer patients who fail to respond to radiotherapy for brain metastases.
abstract: Survival and treatment options are limited for patients with brain metastases arising from non-small cell lung cancer (NSCLC). We evaluated erlotinib and gefitinib as salvage treatments for NSCLC patients with brain metastases that failed to respond to radiotherapy in a retrospective study. Survival was estimated using Kaplan-Meier analysis and log-rank tests. Multivariable predictors were assessed using the Cox proportional hazards model. Epidermal growth factor receptor (EGFR) mutations were assessed in part using sequencing methods. The 103 NSCLC patients who were treated with gefitinib or erlotinib for salvage treatment for brain metastases between January 2005 and December 2011 had overall objective response rates (ORR) of 11.7%, disease control rates (DCR) of 53.4%, 3.6 months of median progression-free survival (PFS), and 7.5 months of median survival. Intracranial disease had an ORR of 11.7% and a DCR of 70.9%. Extracranial disease had an ORR of 8.7% and a DCR of 66.0%. Nine patients (of 22 tested) were documented with EGFR mutations (five with deletion in exon 19 and four with L858R in exon 21). The median PFS for EGFR mutation patients was 9.0 months, versus 3.1 months for wild-type patients (p=0.001). The recursive partitioning analysis class was the only factor predictive of PFS using univariate analyses and was associated with survival in the multivariate analysis. Our retrospective data suggest a potential role for gefitinib and erlotinib in advanced NSCLC patients with brain metastases which have failed to respond to radiotherapy. Patients with EGFR mutations benefited most from treatment.
authors.affiliation: Department of Chemotherapy, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou 310022, China; Key Laboratory, Diagnosis and Treatment Technology on Thoracic Oncology, Zhejiang Province, Hangzhou, China.
authors.forename: Zhengbo
authors.initials: Z
authors.lastname: Song
authors.affiliation: Department of Chemotherapy, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou 310022, China; Key Laboratory, Diagnosis and Treatment Technology on Thoracic Oncology, Zhejiang Province, Hangzhou, China. Electronic address: yipingzhang@yahoo.cn.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000532:radiotherapy / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000532:radiotherapy / Q000556:secondary; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D005260:Female; D005500:Follow-Up Studies; D000077156:Gefitinib; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D016879:Salvage Therapy; D017211:Treatment Failure
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: Brain metastases; EGFR-TKI; Efficacy; Non-small cell lung cancer