PMID- 23516098
OWN - NLM
STAT- MEDLINE
DCOM- 20140130
LR  - 20211021
IS  - 1776-260X (Electronic)
IS  - 1776-2596 (Linking)
VI  - 8
IP  - 2
DP  - 2013 Jun
TI  - Comparison of the efficacy and safety of single-agent erlotinib and doublet 
      molecular targeted agents based on erlotinib in advanced non-small cell lung 
      cancer (NSCLC): a systematic review and meta-analysis.
PG  - 107-16
LID - 10.1007/s11523-013-0272-y [doi]
AB  - In patients with advanced non-small cell lung cancer (NSCLC), the benefit-to-risk 
      ratio of doublet-targeted agents versus single agent is not clear. A systematic 
      review and quantitative meta-analysis were, therefore, undertaken to evaluate the 
      available evidence from randomized trials. This study aims to evaluate the 
      efficacy and safety of erlotinib versus doublets (erlotinib plus another targeted 
      agent) in advanced NSCLC and, if adequate data are available, to investigate 
      whether or not predefined patient groups benefit more or less from 
      doublet-targeted therapy based on erlotinib. Medline, Embase, and the Cochrane 
      Central Register of Controlled Trials were searched. Randomized controlled 
      clinical trials were conducted in which any erlotinib was compared with doublets 
      based on erlotinib in patients with NSCLC who had failed to respond to any 
      previous chemotherapy regimen. Two review authors independently selected studies 
      for inclusion in the review and extracted data. A systematic review and 
      meta-analysis based on aggregate data extracted from trial publications were 
      carried out to assess the effectiveness of doublets (erlotinib plus another 
      targeted drug) in NSCLC treatment. The efficacy outcomes were objective response 
      rate (ORR), complete response plus partial response; disease control rate (DCR), 
      complete response plus partial response and stable disease; and 1-year overall 
      survival (OS). The adverse effects (AEs) were also considered. This involved 
      identifying eligible randomized controlled trials (RCTs) and extracting aggregate 
      data from the reports of these RCTs. Hazard ratios were calculated from published 
      summary statistics and then combined to give pooled estimates of treatment 
      efficacy. This meta-analysis comprised five studies including 2,100 patients 
      (mean age 63; 1,224 men and 876 women; 118 stage IIIB and 1,180 stage IV; 441 
      squamous cell cancers, 1,287 adenocarcinomas, and 372 other pathological types). 
      Doublets regimen significantly improved ORR [hazard ratio (HR) 1.49, 1.13-1.98, 
      p < 0.05] and DCR (HR 1.25, 1.12-1.39, p < 0.05) compared with single erlotinib, 
      but 1-year OS was not significantly improved for doublets [HR 1.06; 95 % 
      confidence interval (CI), 0.95-1.18]. All-grade rash, anemia, diarrhea, anorexia, 
      and fatigue were not significantly different between doublet and erlotinib groups 
      (HR 1.25, 0.99-1.58; 0.98, 0.78-1.24; 1.43, 0.97-2.11; 1.18, 0.84-1.65; and 1.23, 
      0.86-1.77, respectively). The total grade of >/=3 AEs was also not significantly 
      different (HR 1.40, 95 % CI 0.97-2.01). Compared with single-agent erlotinib, 
      doublets (erlotinib plus another targeted agent) significantly improve ORR and 
      DCR, but not OS, and induce no significance of more frequent and serious AEs. The 
      benefit-to-risk ratio of doublets in advanced NSCLC may be more favorable than 
      that of single-agent. The results of this systematic review suggest that patients 
      with advanced NSCLC might benefit from doublet-targeted therapy based on 
      erlotinib compared to erlotinib alone. However, an individual patient data 
      systematic review and meta-analysis are needed to give us a more reliable 
      assessment of the size of benefits and to explore whether doublet therapy may be 
      more or less effective for particular types of patients.
FAU - Pan, Gaofeng
AU  - Pan G
AD  - Department of Thoracic and Cardiovascular Surgery, Zhongnan Hospital, Wuhan 
      University, 169 Donghu Road, Wuchang, Wuhan, Hubei, 430071, People's Republic of 
      China.
FAU - Ke, Shaobo
AU  - Ke S
FAU - Zhao, Jinping
AU  - Zhao J
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Review
PT  - Systematic Review
DEP - 20130321
PL  - France
TA  - Target Oncol
JT  - Targeted oncology
JID - 101270595
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Quinazolines)
RN  - DA87705X9K (Erlotinib Hydrochloride)
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols/*adverse effects/*therapeutic use
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/pathology
MH  - Erlotinib Hydrochloride
MH  - Humans
MH  - Lung Neoplasms/*drug therapy/pathology
MH  - Protein Kinase Inhibitors/administration & dosage/adverse effects/therapeutic use
MH  - Quinazolines/administration & dosage/*adverse effects/*therapeutic use
MH  - Randomized Controlled Trials as Topic
EDAT- 2013/03/22 06:00
MHDA- 2014/01/31 06:00
CRDT- 2013/03/22 06:00
PHST- 2012/12/28 00:00 [received]
PHST- 2013/03/10 00:00 [accepted]
PHST- 2013/03/22 06:00 [entrez]
PHST- 2013/03/22 06:00 [pubmed]
PHST- 2014/01/31 06:00 [medline]
AID - 10.1007/s11523-013-0272-y [doi]
PST - ppublish
SO  - Target Oncol. 2013 Jun;8(2):107-16. doi: 10.1007/s11523-013-0272-y. Epub 2013 Mar 
      21.