PMID- 27568322
OWN - NLM
STAT- MEDLINE
DCOM- 20170307
LR  - 20220408
IS  - 1436-3305 (Electronic)
IS  - 1436-3291 (Linking)
VI  - 20
IP  - 1
DP  - 2017 Jan
TI  - Targeted therapies for advanced and metastatic adenocarcinoma of the 
      gastroesophageal junction: is there something new?
PG  - 31-42
LID - 10.1007/s10120-016-0626-0 [doi]
AB  - Despite improvements in systemic chemotherapy (CT), the prognosis of metastatic 
      adenocarcinoma of the gastroesophageal junction remains poor. Over the years, new 
      targeting agents have become available and were tested, with or without CT, in 
      first or subsequent lines of therapy. The epidermal growth factor receptor family 
      was targeted with monoclonal antibodies (MoAbs) (trastuzumab, cetuximab, 
      panitumumab) and tyrosin kinase inhibitors (TKIs) (lapatinib, erlotinib, 
      gefitinib). Only trastuzumab, in combination with cisplatin and 
      fluoropyrimidines, significantly improved overall survival (OS) in first-line 
      therapy (13.8 vs. 11.1 months). Angiogenesis also was targeted with MoAbs 
      (bevacizumab and ramucirumab); ramucirumab, a vascular endothelial growth 
      factor-receptor 2 antagonist, enhanced OS in two phase III studies in the first 
      (9.6 vs. 7.4 months) and subsequent lines of treatment (5.2 vs. 3.8 months), 
      while the bevacizumab study was negative. TKIs (sunitinib, sorafenib, 
      regorafenib, apatinib) were tested in this setting in phase II studies in the 
      second/third line, only showing modest antitumor activity. The hepatocyte growth 
      factor receptor (MET) was targeted in untreated patients in a phase III trial 
      with MoAb rilotumumab, with or without CT, but the study was stopped because of 
      mortality excess in the rilotumumab arm. Mammalian target of rapamycin (MTOR) 
      pathway inhibition with everolimus was tested in pretreated patients in a 
      placebo-controlled phase III trial who failed to improve OS (5.4 vs. 4.3 months). 
      In conclusion, considering the modest survival gain obtained overall, the high 
      cost of these therapies and the quality of life issue must be primarily 
      considered in treating these patients.
FAU - Pasini, Felice
AU  - Pasini F
AD  - Department of Medical Oncology, Ospedale S. Maria della Misericordia, Viale Tre 
      Martiri, 140-45100, Rovigo, Italy. felicepasini@excite.com.
FAU - Fraccon, Anna Paola
AU  - Fraccon AP
AD  - Medical Oncology Unit, Casa di Cura Pederzoli, Peschiera del Garda, Verona, 
      Italy.
FAU - Modena, Yasmina
AU  - Modena Y
AD  - Department of Medical Oncology, Ospedale S. Maria della Misericordia, Viale Tre 
      Martiri, 140-45100, Rovigo, Italy.
FAU - Bencivenga, Maria
AU  - Bencivenga M
AD  - General and Upper GI Surgery Division, University of Verona, Verona, Italy.
FAU - Giacopuzzi, Simone
AU  - Giacopuzzi S
AD  - General and Upper GI Surgery Division, University of Verona, Verona, Italy.
FAU - La Russa, Francesca
AU  - La Russa F
AD  - Department of Medical Oncology, Ospedale S. Maria della Misericordia, Viale Tre 
      Martiri, 140-45100, Rovigo, Italy.
FAU - Gusella, Milena
AU  - Gusella M
AD  - Department of Medical Oncology, Ospedale S. Maria della Misericordia, Viale Tre 
      Martiri, 140-45100, Rovigo, Italy.
FAU - de Manzoni, Giovanni
AU  - de Manzoni G
AD  - General and Upper GI Surgery Division, University of Verona, Verona, Italy.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20160827
PL  - Japan
TA  - Gastric Cancer
JT  - Gastric cancer : official journal of the International Gastric Cancer Association 
      and the Japanese Gastric Cancer Association
JID - 100886238
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Neoplasm Proteins)
SB  - IM
MH  - Adenocarcinoma/*drug therapy/metabolism/secondary
MH  - Antineoplastic Agents/*therapeutic use
MH  - Esophageal Neoplasms/*drug therapy/metabolism/pathology
MH  - Esophagogastric Junction/*drug effects/metabolism/pathology
MH  - Humans
MH  - *Molecular Targeted Therapy
MH  - Neoplasm Proteins/*antagonists & inhibitors/metabolism
MH  - Stomach Neoplasms/*drug therapy/metabolism/pathology
OTO - NOTNLM
OT  - Advanced disease
OT  - Gastroesophageal junction adenocarcinoma
OT  - Targeted therapies
EDAT- 2016/08/29 06:00
MHDA- 2017/03/08 06:00
CRDT- 2016/08/29 06:00
PHST- 2016/01/03 00:00 [received]
PHST- 2016/08/02 00:00 [accepted]
PHST- 2016/08/29 06:00 [pubmed]
PHST- 2017/03/08 06:00 [medline]
PHST- 2016/08/29 06:00 [entrez]
AID - 10.1007/s10120-016-0626-0 [pii]
AID - 10.1007/s10120-016-0626-0 [doi]
PST - ppublish
SO  - Gastric Cancer. 2017 Jan;20(1):31-42. doi: 10.1007/s10120-016-0626-0. Epub 2016 
      Aug 27.