title: Randomized trial of erlotinib plus whole-brain radiotherapy for NSCLC patients with multiple brain metastases.
abstract: BACKGROUND
  Median survival of non-small cell lung cancer (NSCLC) patients with brain metastases is poor. We examined concurrent erlotinib and whole brain radiotherapy (WBRT) followed by maintenance erlotinib in patients with untreated brain metastases, given the potential radiosensitizing properties of erlotinib and its direct effect on brain metastases and systemic activity.
  
  
  METHODS
  Eighty NSCLC patients with KPS of 70 and greater and multiple brain metastases were randomly assigned to placebo (n = 40) or erlotinib (100mg, n = 40) given concurrently with WBRT (20 Gy in 5 fractions). Following WBRT, patients continued with placebo or erlotinib (150 mg) until disease progression. The primary end point was neurological progression-free survival (nPFS); hazard ratios (HRs) were calculated using Cox regression. All P values were two-sided.
  
  
  RESULTS
  Fifteen patients (37.5%) from each arm were alive and without neurological progression 2 months after WBRT. Median nPFS was 1.6 months in both arms; nPFS HR 0.95 (95% CI = 0.59 to 1.54; P = .84). Median overall survival (OS) was 2.9 and 3.4 months in the placebo and erlotinib arms; HR 0.95 (95% CI = 0.58 to 1.55; P = .83). The frequency of epidermal growth factor receptor (EGFR) mutations was low with only 1 of 35 (2.9%) patients with available samples had activating EGFR-mutations. Grade 3/4 adverse event rates were similar between the two groups (70.0% in each arm), except for rash 20.0% (erlotinib) vs 5.0% (placebo), and fatigue 17.5% vs 35.0%. No statistically significant quality of life differences were found.
  
  
  CONCLUSIONS
  Our study showed no advantage in nPFS or OS for concurrent erlotinib and WBRT followed by maintenance erlotinib in patients with predominantly EGFR wild-type NSCLC and multiple brain metastases compared to placebo. Future studies should focus on the role of erlotinib with or without WBRT in patients with EGFR mutations.
authors.affiliation: Affiliations of authors: Department of Oncology, University College London (UCL) Cancer Institute and UCL Hospitals, London, UK (SML, NP); Department of Oncology, Charing Cross Hospital, London, UK (CRL); Cancer Research UK and UCL Cancer Trials Centre, UCL Cancer Institute, London, UK (NC, CW, YN, AH); Department of Oncology, Southampton General Hospital, Southampton, UK (CO, AB); Radiotherapy Related Research, The Christie NHS Foundation Trust, Manchester (CFF), UK. sm.lee@uclh.nhs.uk.
authors.forename: Siow Ming
authors.initials: SM
authors.lastname: Lee
authors.affiliation: Affiliations of authors: Department of Oncology, University College London (UCL) Cancer Institute and UCL Hospitals, London, UK (SML, NP); Department of Oncology, Charing Cross Hospital, London, UK (CRL); Cancer Research UK and UCL Cancer Trials Centre, UCL Cancer Institute, London, UK (NC, CW, YN, AH); Department of Oncology, Southampton General Hospital, Southampton, UK (CO, AB); Radiotherapy Related Research, The Christie NHS Foundation Trust, Manchester (CFF), UK.
authors.forename: Conrad R
authors.initials: CR
authors.lastname: Lewanski
authors.affiliation: Affiliations of authors: Department of Oncology, University College London (UCL) Cancer Institute and UCL Hospitals, London, UK (SML, NP); Department of Oncology, Charing Cross Hospital, London, UK (CRL); Cancer Research UK and UCL Cancer Trials Centre, UCL Cancer Institute, London, UK (NC, CW, YN, AH); Department of Oncology, Southampton General Hospital, Southampton, UK (CO, AB); Radiotherapy Related Research, The Christie NHS Foundation Trust, Manchester (CFF), UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Counsell
authors.affiliation: Affiliations of authors: Department of Oncology, University College London (UCL) Cancer Institute and UCL Hospitals, London, UK (SML, NP); Department of Oncology, Charing Cross Hospital, London, UK (CRL); Cancer Research UK and UCL Cancer Trials Centre, UCL Cancer Institute, London, UK (NC, CW, YN, AH); Department of Oncology, Southampton General Hospital, Southampton, UK (CO, AB); Radiotherapy Related Research, The Christie NHS Foundation Trust, Manchester (CFF), UK.
authors.forename: Christian
authors.initials: C
authors.lastname: Ottensmeier
authors.affiliation: Affiliations of authors: Department of Oncology, University College London (UCL) Cancer Institute and UCL Hospitals, London, UK (SML, NP); Department of Oncology, Charing Cross Hospital, London, UK (CRL); Cancer Research UK and UCL Cancer Trials Centre, UCL Cancer Institute, London, UK (NC, CW, YN, AH); Department of Oncology, Southampton General Hospital, Southampton, UK (CO, AB); Radiotherapy Related Research, The Christie NHS Foundation Trust, Manchester (CFF), UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bates
authors.affiliation: Affiliations of authors: Department of Oncology, University College London (UCL) Cancer Institute and UCL Hospitals, London, UK (SML, NP); Department of Oncology, Charing Cross Hospital, London, UK (CRL); Cancer Research UK and UCL Cancer Trials Centre, UCL Cancer Institute, London, UK (NC, CW, YN, AH); Department of Oncology, Southampton General Hospital, Southampton, UK (CO, AB); Radiotherapy Related Research, The Christie NHS Foundation Trust, Manchester (CFF), UK.
authors.forename: Nirali
authors.initials: N
authors.lastname: Patel
authors.affiliation: Affiliations of authors: Department of Oncology, University College London (UCL) Cancer Institute and UCL Hospitals, London, UK (SML, NP); Department of Oncology, Charing Cross Hospital, London, UK (CRL); Cancer Research UK and UCL Cancer Trials Centre, UCL Cancer Institute, London, UK (NC, CW, YN, AH); Department of Oncology, Southampton General Hospital, Southampton, UK (CO, AB); Radiotherapy Related Research, The Christie NHS Foundation Trust, Manchester (CFF), UK.
authors.forename: Christina
authors.initials: C
authors.lastname: Wadsworth
authors.affiliation: Affiliations of authors: Department of Oncology, University College London (UCL) Cancer Institute and UCL Hospitals, London, UK (SML, NP); Department of Oncology, Charing Cross Hospital, London, UK (CRL); Cancer Research UK and UCL Cancer Trials Centre, UCL Cancer Institute, London, UK (NC, CW, YN, AH); Department of Oncology, Southampton General Hospital, Southampton, UK (CO, AB); Radiotherapy Related Research, The Christie NHS Foundation Trust, Manchester (CFF), UK.
authors.forename: Yenting
authors.initials: Y
authors.lastname: Ngai
authors.affiliation: Affiliations of authors: Department of Oncology, University College London (UCL) Cancer Institute and UCL Hospitals, London, UK (SML, NP); Department of Oncology, Charing Cross Hospital, London, UK (CRL); Cancer Research UK and UCL Cancer Trials Centre, UCL Cancer Institute, London, UK (NC, CW, YN, AH); Department of Oncology, Southampton General Hospital, Southampton, UK (CO, AB); Radiotherapy Related Research, The Christie NHS Foundation Trust, Manchester (CFF), UK.
authors.forename: Allan
authors.initials: A
authors.lastname: Hackshaw
authors.affiliation: Affiliations of authors: Department of Oncology, University College London (UCL) Cancer Institute and UCL Hospitals, London, UK (SML, NP); Department of Oncology, Charing Cross Hospital, London, UK (CRL); Cancer Research UK and UCL Cancer Trials Centre, UCL Cancer Institute, London, UK (NC, CW, YN, AH); Department of Oncology, Southampton General Hospital, Southampton, UK (CO, AB); Radiotherapy Related Research, The Christie NHS Foundation Trust, Manchester (CFF), UK.
authors.forename: Corinne
authors.initials: C
authors.lastname: Faivre-Finn
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000503:physiopathology / Q000532:radiotherapy* / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000532:radiotherapy* / Q000556:secondary; D017024:Chemotherapy, Adjuvant; D016371:Cranial Irradiation / Q000009:adverse effects; D018572:Disease-Free Survival; D004311:Double-Blind Method; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use*; D020127:Recovery of Function; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors