Supervisors info:
Ζαγουρή Φλώρα, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ, Επιβλέπουσα
Τέρπος Ευάγγελος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Σταματελόπουλος Κίμων, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Summary:
Gastric cancer is one of the most prevalent and lethal malignancies. The prognosis of patients with advanced/metastatic disease is poor as chemotherapy has only modest efficacy in prolonging survival. Recently, molecularly-targeted therapies for HER2-positive gastric cancer have become available, however the efficacy and safety of many of these still remain inconclusive.
We systematically reviewed the literature to summarize clinical data and evaluate the efficacy and safety of HER2-targeted therapies for inoperable and/or metastatic gastric and gastroesophageal junction cancer (GC/GJC). We searched Medline/Pubmed, Scopus, CENTRAL, clinicaltrials.gov, ASCO and ESMO meetings’ abstracts up to November 30th 2018 to identify prospective studies fulfilling specific criteria. We also searched the reference lists of included studies.
In all, 42 studies were included of which 27 utilized trastuzumab, 5 lapatinib, 2 pertuzumab, 2 margetuximab and one each, trastuzumab-emtasine, afatinib, dacomitinib, MCLA-128, MM-111, AZD8931. Most of the studies (n=28) were phase 2 trials. The majority of them were non-randomized (n=30), 28 were uncontrolled, 3 were double-blind, and only 4 were placebo- controlled. Twenty five used anti-HER2 agents as 1st line or beyond treatment and 17 as 2nd line or beyond. With the exception of the ToGA trial, all other major clinical trials failed to achieve their primary end points.
Up to date, trastuzumab combined with chemotherapy constitutes the only evidenced-based effective HER2-targeted therapy for patients with unresectable/metastatic GC/GJC. Despite extensive research, no other anti-HER2 therapy was found to prolong survival in these patients. However, promising results exist for some agents and warrant further evaluation in larger studies.
Keywords:
Stomach, Adenocarcinoma, Targeted therapies, HER2, Systematic review
