title: Targeted therapies for advanced and metastatic adenocarcinoma of the gastroesophageal junction: is there something new?
abstract: 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.
authors: Department of Medical Oncology, Ospedale S. Maria della Misericordia, Viale Tre Martiri, 140-45100, Rovigo, Italy. felicepasini@excite.com.
authors: Felice
authors: F
authors: Pasini
authors: Medical Oncology Unit, Casa di Cura Pederzoli, Peschiera del Garda, Verona, Italy.
authors: Anna Paola
authors: AP
authors: Fraccon
authors: Department of Medical Oncology, Ospedale S. Maria della Misericordia, Viale Tre Martiri, 140-45100, Rovigo, Italy.
authors: Yasmina
authors: Y
authors: Modena
authors: General and Upper GI Surgery Division, University of Verona, Verona, Italy.
authors: Maria
authors: M
authors: Bencivenga
authors: General and Upper GI Surgery Division, University of Verona, Verona, Italy.
authors: Simone
authors: S
authors: Giacopuzzi
authors: Department of Medical Oncology, Ospedale S. Maria della Misericordia, Viale Tre Martiri, 140-45100, Rovigo, Italy.
authors: Francesca
authors: F
authors: La Russa
authors: Department of Medical Oncology, Ospedale S. Maria della Misericordia, Viale Tre Martiri, 140-45100, Rovigo, Italy.
authors: Milena
authors: M
authors: Gusella
authors: General and Upper GI Surgery Division, University of Verona, Verona, Italy.
authors: Giovanni
authors: G
authors: de Manzoni
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004943:Esophagogastric Junction / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins
keywords: Advanced disease; Gastroesophageal junction adenocarcinoma; Targeted therapies