Assessment of Ramucirumab plus paclitaxel as switch maintenance versus continuation of first-line chemotherapy in patients with advanced HER-2 negative gastric or gastroesophageal junction cancers: the ARMANI phase III trial

BMC Cancer

Libero Ciuffreda¹  Mario Scartozzi²  Francesco Di Costanzo³  Rossana Berardi⁴  Giorgio Scagliotti⁵  Andrea Spallanzani⁶  Giampaolo Tortora⁷  Alessandro Bertolini⁸  Vincenzo Catalano⁹  Giovanni Gerardo Cardellino^1,10  Evaristo Maiello^1,11  Salvatore Corallo^1,12  Filippo Pietrantonio^1,12  Marta Caporale^1,12  Monica Niger^1,12  Maria Di Bartolomeo^1,12  Federica Morano^1,12  Filippo de Braud^1,12  Maria Antista^1,12  Alberto Zaniboni^1,13  Michele Basso^1,14  Francesco Giuliani^1,15  Sara Lonardi^1,16  Alberto Gianluigi Luporini^1,17  Giovanni Luca Frassineti^1,18  Stefano Tamberi^1,19  Saverio Cinieri^2,20  Andrea Bonetti^2,21  Sergio Bracarda^2,22  Raffaella Longarini^2,23  Davide Tassinari^2,24  Graziella Pinotti^2,25  Gianluca Tomasello^2,26  Hector Soto Parra^2,27  Lorenzo Fornaro^2,27  Claudio Verusio^2,27  Ferdinando De Vita^2,28  Lorenza Rimassa^2,29  Samantha Di Donato^3,30 

[1] Department of Medical Oncology, A.O.U. Citta della Salute e della Scienza di Torino;Department of Medical Oncology, AOU Cagliari;Department of Medical Oncology, AOU Careggi di Firenze;Department of Medical Oncology, AOU Ospedali Riuniti Di Ancona;Department of Medical Oncology, AOU San Luigi Gonzaga;Department of Medical Oncology, AOU di Modena;Department of Medical Oncology, AOUI Verona Ospedale Policlinico ‘Giambattista Rossi’ di Borgo Roma;Department of Medical Oncology, ASST della Valtellina e dell’Alto Lario;Department of Medical Oncology, Azienda Ospedaliera “Ospedali Riuniti Marche Nord”;Department of Medical Oncology, Azienda Sanitaria Universitaria Integrata di Udine;Department of Medical Oncology, Casa Sollievo della Sofferenza;Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori;Department of Medical Oncology, Fondazione Poliambulanza;Department of Medical Oncology, Fondazione Policlinico Universitario “A. Gemelli” - IRCCS, Università Cattolica del Sacro Cuore;Department of Medical Oncology, I.R.C.C.S. Istituto Tumori Bari;Department of Medical Oncology, IOV Istituto Oncologico Veneto;Department of Medical Oncology, IRCCS Policlinico San Donato;Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS;Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST);Department of Medical Oncology, Ospedale A. Perrino di Brindisi;Department of Medical Oncology, Ospedale Mater Salutis;Department of Medical Oncology, Ospedale San Donato;Department of Medical Oncology, Ospedale San Gerardo;Department of Medical Oncology, Ospedale degli infermi di Rimini;Department of Medical Oncology, Ospedale di Circolo e Fondazione Macchi;Department of Medical Oncology, Ospedale di Cremona;Department of Medical Oncology;Division of Medical Oncology, Department of Precision Medicine, University of Campania ‘Luigi Vanvitelli’ - School of Medicine;Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center;Sandro Pitigliani Medical Oncology Department, Nuovo Ospedale di Prato;

关键词: Metastatic gastric cancer;    First line;    Maintenance;    Ramucirumab;    Clinical trial;   

DOI  :  10.1186/s12885-019-5498-3

来源: DOAJ

【 摘 要 】

Abstract Background Platinum/fluoropyrimidine regimens are the backbone of first-line chemotherapy for advanced gastric cancer (AGC). However response rates to first line chemotherapy range from 30 to 50% and disease progression occurs after 4–6 cycles. The optimal duration of first-line therapy is still unknown and its continuation until disease progression represents the standard. However this strategy is often associated with cumulative toxicity and rapid development of drug resistance. Moreover, only about 40% of AGC pts. are eligible for second-line treatment. Methods This is a randomized, open-label, multicenter phase III trial. It aims at assessing whether switch maintenance to ramucirumab plus paclitaxel will extend the progression-free survival (PFS) of subjects with HER-2 negative AGC who have not progressed after 3 months of a first-line with a platinum/fluoropyrimidine regimen (either FOLFOX4, mFOLFOX6 or XELOX). The primary endpoint is to compare Progression-Free Survival (PFS) of patients in ARM A (switch maintenance to ramucirumab and placlitaxel) versus ARM B (continuation of the same first-line therapy with oxaliplatin/fluoropyrimidine). Secondary endpoints are: overall survival, time-to-treatment failure, overall response rate, duration of response, percentage of patients that will receive a second line therapy according to arm treatment, safety, quality of life. Exploratory studies including Next-Generation Sequencing (NGS) in archival tumor tissues are planned in order to identify potential biomarkers of primary resistance and prognosis. Discussion The ARMANI study estimates if patients treated with early swich with ramucirumab plus paclitaxel received benefit when compared to those treated with continuation of first line therapy. The hypothesis is that the early administration of an active, non-cross resistant second-line regimen such as ramucirumab plus paclitaxel may prolong the time in which patients are progression-free, and consequently have a better quality of life. Moreover, this strategy may rescue all those subjects that become ineligible for second-line therapy due to the rapid deterioration of health status after the first disease progression. Trial registration ARMANI is registered at ClinicalTrials.gov (NCT02934464, October 17, 2016) and EudraCT(2016–001783-12, April 202,016).

【 授权许可】

Unknown