title: Monoclonal antibodies for treating gastric cancer: promises and pitfalls.
abstract: Gastric cancer (GC) presents dismal prognosis when diagnosed at advanced stages, standard chemotherapy having shown little efficacy. Introduction of biotherapies interfering with novel targets and signaling pathways is currently an emerging strategy.
  
  
  
  Only two monoclonal antibodies (trastuzumab and ramucirumab) have been approved, mostly in association with cytotoxics. Conversely, testing other promising biotherapies (panitumumab, cetuximab, bevacizumab, rilotumumab) have yielded conflicting results, since encouraging early clinical trials have failed to be confirmed in larger phase-III studies. Empirical and underpowered strategies when designing combinational studies, lack of comprehensive knowledge of pharmacokinetics/pharmacodynamics (PK/PD) relationships, and underestimation of the large inter-patient variability in drug exposure levels with monoclonal antibodies, could explain the failures in developing biotherapies in gastric cancer. This review covers the achievements and limits of monoclonal antibodies in gastric cancer and proposes clues to overcome current failures.
  
  
  
  Trastuzumab efficacy could be improved thanks to its combination with triplet chemotherapy or with another anti-HER2 agents or in continuation during second-line chemotherapy. Concerning ramucirumab, further studies are necessary to prove its interest in first line treatment of advanced GC, to use the optimal dose in each patient-given the large inter-patients variability, and to find predictive biomarkers of efficacy.
authors.affiliation: a Department of Digestive Oncology , Aix-Marseille University - Assistance Publique Hôpitaux de Marseille , Marseille , France.
authors.forename: Camille
authors.initials: C
authors.lastname: Sibertin-Blanc
authors.affiliation: b Laboratoire de Pharmacocinétique , SMARTc Inserm S_911 CRO2 Aix Marseille University , Marseille , France.
authors.forename: Joseph
authors.initials: J
authors.lastname: Ciccolini
authors.affiliation: a Department of Digestive Oncology , Aix-Marseille University - Assistance Publique Hôpitaux de Marseille , Marseille , France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Norguet
authors.affiliation: b Laboratoire de Pharmacocinétique , SMARTc Inserm S_911 CRO2 Aix Marseille University , Marseille , France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Lacarelle
authors.affiliation: a Department of Digestive Oncology , Aix-Marseille University - Assistance Publique Hôpitaux de Marseille , Marseille , France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Dahan
authors.affiliation: a Department of Digestive Oncology , Aix-Marseille University - Assistance Publique Hôpitaux de Marseille , Marseille , France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Seitz
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab / Q000627:therapeutic use; D002986:Clinical Trials as Topic / Q000379:methods; D006801:Humans; D000077544:Panitumumab; D011379:Prognosis; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000276:immunology; D016896:Treatment Outcome; D000096662:Ramucirumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D000077544:Panitumumab; D000096662:Ramucirumab; C524459:rilotumumab
keywords: Gastric cancer; bevacizumab; monoclonal antibody; ramucirumab; trastuzumab