PMID- 27511219
OWN - NLM
STAT- MEDLINE
DCOM- 20170713
LR  - 20220408
IS  - 1532-2807 (Electronic)
IS  - 1219-4956 (Linking)
VI  - 23
IP  - 2
DP  - 2017 Apr
TI  - Variations in EGFR ctDNA Correlates to the Clinical Efficacy of Afatinib in Non 
      Small Cell Lung Cancer with Acquired Resistance.
PG  - 307-315
LID - 10.1007/s12253-016-0097-y [doi]
AB  - Monitoring of non small cell lung cancer (NSCLC) patients on afatinib after 
      acquired resistance to 1(st) generation tyrosine kinase inhibitors is important. 
      Circulating tumor DNA (ctDNA) offers an attractive means other than conventional 
      tissue biopsy to characterize real time dynamic changes of the disease. In our 
      study, we aim to ascertain the clinical value for ctDNA monitoring of NSCLC 
      patients with acquired resistance for afatinib treatment. 200 patients positive 
      for the activating epithermal growth factor receptor (EGFR) mutations were 
      recruited for the study. Baseline molecular profiling for L858R, Exon 19 deletion 
      and T790M were performed. Thereafter, serial blood samples were taken and 
      patients were assessed by overall survival (OS) to determine the usefulness of 
      ctDNA monitoring. At baseline, matched tumor biopsy and ctDNA analysis had a 
      concordance agreement of 93.5% for L858R and exon 19 deletion. We also determined 
      that a large proportion of patients had the drug resistance mutation T790M prior 
      to starting afatinib and these patients were linked to a worse survival outcome. 
      For patients that registered a drop in ctDNA levels after afatinib was 
      administered, we observed that their survival outcome was more favorable (hazard 
      ratio 1.56, (95% CI 1.04 to 2.43). ctDNA levels were mostly elevated after the 
      3(rd) sampling cycle. Our results suggest that ctDNA can be used to predict the 
      clinical benefits of afatinib treatment. Pre and post blood sampling aids to 
      identify patient groups that may benefit most from the treatment and ctDNA is 
      relatively sensitive to address the dynamic changes of the disease at the 
      molecular level.
FAU - He, Jinfeng
AU  - He J
AD  - Department of Respiratory Medicine, Jingzhou Central Hospital, The Second 
      Clinical Medical College, Yangtze University, Renmin Road 1, 434020, Jingzhou, 
      People's Republic of China.
FAU - Tan, Wei
AU  - Tan W
AD  - Haemodialysis Centre, Jingzhou Central Hospital, The Second Clinical Medical 
      College, Yangtze University, Jingzhou, People's Republic of China.
FAU - Tang, Xuelian
AU  - Tang X
AD  - Department of Respiratory Medicine, Jingzhou Central Hospital, The Second 
      Clinical Medical College, Yangtze University, Renmin Road 1, 434020, Jingzhou, 
      People's Republic of China.
FAU - Ma, Jingping
AU  - Ma J
AD  - Department of Respiratory Medicine, Jingzhou Central Hospital, The Second 
      Clinical Medical College, Yangtze University, Renmin Road 1, 434020, Jingzhou, 
      People's Republic of China. mjpjzhospital@hotmail.com.
LA  - eng
PT  - Journal Article
DEP - 20160811
PL  - Switzerland
TA  - Pathol Oncol Res
JT  - Pathology oncology research : POR
JID - 9706087
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (DNA, Neoplasm)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Quinazolines)
RN  - 41UD74L59M (Afatinib)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Afatinib
MH  - Biomarkers, Tumor/blood/genetics
MH  - Carcinoma, Non-Small-Cell Lung/blood/*drug therapy/genetics
MH  - DNA, Neoplasm/*blood
MH  - Drug Resistance, Neoplasm/*genetics
MH  - ErbB Receptors/*genetics
MH  - Female
MH  - Humans
MH  - Lung Neoplasms/blood/*drug therapy/genetics
MH  - Male
MH  - Middle Aged
MH  - Mutation/genetics
MH  - Protein Kinase Inhibitors/*therapeutic use
MH  - Quinazolines/*therapeutic use
OTO - NOTNLM
OT  - Acquired resistance
OT  - Afatinib
OT  - EGFR mutations
OT  - Non small cell lung cancer (NSCLC)
OT  - ctDNA
EDAT- 2016/08/12 06:00
MHDA- 2017/07/14 06:00
CRDT- 2016/08/12 06:00
PHST- 2016/05/23 00:00 [received]
PHST- 2016/07/28 00:00 [accepted]
PHST- 2016/08/12 06:00 [pubmed]
PHST- 2017/07/14 06:00 [medline]
PHST- 2016/08/12 06:00 [entrez]
AID - 10.1007/s12253-016-0097-y [pii]
AID - 10.1007/s12253-016-0097-y [doi]
PST - ppublish
SO  - Pathol Oncol Res. 2017 Apr;23(2):307-315. doi: 10.1007/s12253-016-0097-y. Epub 
      2016 Aug 11.