title: Systemic therapy beyond first-line in advanced gastric cancer: An overview of the main randomized clinical trials.
abstract: Following progression on first-line platinum and fluoropyrimidine-based chemotherapy, prognosis for advanced gastric cancer patients is extremely poor. Thus, new and effective treatments are required. Based on positive results of recent randomized controlled trials, second-line monochemotherapies with either irinotecan or taxanes confer a median overall survival of approximately 5 months in gastro-esophageal and gastric adenocarcinoma. Combination of weekly paclitaxel and ramucirumab, a novel anti-angiogenic VEGFR2 antibody, pushes the overall survival up to over 9.5 months, whereas apatinib, a novel oral VEGFR2 tyrosine kinase inhibitor, seems to be promising in heavily pretreated patients. In contrast, the role of EGFR/HER2 and mTOR inhibitors is controversial. Studies are heterogeneous for tumor population, geographical areas, quality of life assessment, type of first-line therapy and response to that, making clinical practice application of the trial results difficult. Furthermore, sustainability is challenging due to high cost of novel biotherapies.
authors.affiliation: Gastrointestinal Medical Oncology and Neuroendocrine Tumors Unit European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy. Electronic address: salvatore.galdy@ieo.it.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Galdy
authors.affiliation: Gastrointestinal Medical Oncology and Neuroendocrine Tumors Unit European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
authors.forename: Chiara Alessandra
authors.initials: CA
authors.lastname: Cella
authors.affiliation: Gastrointestinal Medical Oncology and Neuroendocrine Tumors Unit European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Spada
authors.affiliation: Gastrointestinal Medical Oncology and Neuroendocrine Tumors Unit European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
authors.forename: Sabina
authors.initials: S
authors.lastname: Murgioni
authors.affiliation: Gastrointestinal Medical Oncology and Neuroendocrine Tumors Unit European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Frezza
authors.affiliation: Gastrointestinal Medical Oncology and Neuroendocrine Tumors Unit European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
authors.forename: Simona Paola
authors.initials: SP
authors.lastname: Ravenda
authors.affiliation: Gastrointestinal Medical Oncology and Neuroendocrine Tumors Unit European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
authors.forename: Maria Giulia
authors.initials: MG
authors.lastname: Zampino
authors.affiliation: Gastrointestinal Medical Oncology and Neuroendocrine Tumors Unit European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Fazio
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant / Q000379:methods* / Q000592:standards / Q000706:statistics & numerical data; D018450:Disease Progression; D006801:Humans; D020360:Neoadjuvant Therapy; D017239:Paclitaxel / Q000008:administration & dosage; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic / Q000592:standards / Q000706:statistics & numerical data; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D017239:Paclitaxel
keywords: Advanced gastric cancer; Molecular targeted agents; Randomized controlled trials; Second-line chemotherapy