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
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...
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2019-03-01
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Online Access: | http://link.springer.com/article/10.1186/s12885-019-5498-3 |
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author |
Maria Di Bartolomeo Monica Niger Federica Morano Salvatore Corallo Maria Antista Stefano Tamberi Sara Lonardi Samantha Di Donato Rossana Berardi Mario Scartozzi Giovanni Gerardo Cardellino Francesco Di Costanzo Lorenza Rimassa Alberto Gianluigi Luporini Raffaella Longarini Alberto Zaniboni Alessandro Bertolini Gianluca Tomasello Graziella Pinotti Giorgio Scagliotti Giampaolo Tortora Andrea Bonetti Andrea Spallanzani Giovanni Luca Frassineti Davide Tassinari Francesco Giuliani Saverio Cinieri Evaristo Maiello Claudio Verusio Sergio Bracarda Vincenzo Catalano Michele Basso Libero Ciuffreda Ferdinando De Vita Hector Soto Parra Lorenzo Fornaro Marta Caporale Filippo de Braud Filippo Pietrantonio |
spellingShingle |
Maria Di Bartolomeo Monica Niger Federica Morano Salvatore Corallo Maria Antista Stefano Tamberi Sara Lonardi Samantha Di Donato Rossana Berardi Mario Scartozzi Giovanni Gerardo Cardellino Francesco Di Costanzo Lorenza Rimassa Alberto Gianluigi Luporini Raffaella Longarini Alberto Zaniboni Alessandro Bertolini Gianluca Tomasello Graziella Pinotti Giorgio Scagliotti Giampaolo Tortora Andrea Bonetti Andrea Spallanzani Giovanni Luca Frassineti Davide Tassinari Francesco Giuliani Saverio Cinieri Evaristo Maiello Claudio Verusio Sergio Bracarda Vincenzo Catalano Michele Basso Libero Ciuffreda Ferdinando De Vita Hector Soto Parra Lorenzo Fornaro Marta Caporale Filippo de Braud Filippo Pietrantonio 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 Metastatic gastric cancer First line Maintenance Ramucirumab Clinical trial |
author_facet |
Maria Di Bartolomeo Monica Niger Federica Morano Salvatore Corallo Maria Antista Stefano Tamberi Sara Lonardi Samantha Di Donato Rossana Berardi Mario Scartozzi Giovanni Gerardo Cardellino Francesco Di Costanzo Lorenza Rimassa Alberto Gianluigi Luporini Raffaella Longarini Alberto Zaniboni Alessandro Bertolini Gianluca Tomasello Graziella Pinotti Giorgio Scagliotti Giampaolo Tortora Andrea Bonetti Andrea Spallanzani Giovanni Luca Frassineti Davide Tassinari Francesco Giuliani Saverio Cinieri Evaristo Maiello Claudio Verusio Sergio Bracarda Vincenzo Catalano Michele Basso Libero Ciuffreda Ferdinando De Vita Hector Soto Parra Lorenzo Fornaro Marta Caporale Filippo de Braud Filippo Pietrantonio |
author_sort |
Maria Di Bartolomeo |
title |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
BMC |
series |
BMC Cancer |
issn |
1471-2407 |
publishDate |
2019-03-01 |
description |
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). |
topic |
Metastatic gastric cancer First line Maintenance Ramucirumab Clinical trial |
url |
http://link.springer.com/article/10.1186/s12885-019-5498-3 |
work_keys_str_mv |
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doaj-d0e8c64069684a23a1a693ea53c572e02020-11-25T03:03:26ZengBMCBMC Cancer1471-24072019-03-011911910.1186/s12885-019-5498-3Assessment 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 trialMaria Di Bartolomeo0Monica Niger1Federica Morano2Salvatore Corallo3Maria Antista4Stefano Tamberi5Sara Lonardi6Samantha Di Donato7Rossana Berardi8Mario Scartozzi9Giovanni Gerardo Cardellino10Francesco Di Costanzo11Lorenza Rimassa12Alberto Gianluigi Luporini13Raffaella Longarini14Alberto Zaniboni15Alessandro Bertolini16Gianluca Tomasello17Graziella Pinotti18Giorgio Scagliotti19Giampaolo Tortora20Andrea Bonetti21Andrea Spallanzani22Giovanni Luca Frassineti23Davide Tassinari24Francesco Giuliani25Saverio Cinieri26Evaristo Maiello27Claudio Verusio28Sergio Bracarda29Vincenzo Catalano30Michele Basso31Libero Ciuffreda32Ferdinando De Vita33Hector Soto Parra34Lorenzo Fornaro35Marta Caporale36Filippo de Braud37Filippo Pietrantonio38Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale TumoriDepartment of Medical Oncology, Fondazione IRCCS Istituto Nazionale TumoriDepartment of Medical Oncology, Fondazione IRCCS Istituto Nazionale TumoriDepartment of Medical Oncology, Fondazione IRCCS Istituto Nazionale TumoriDepartment of Medical Oncology, Fondazione IRCCS Istituto Nazionale TumoriDepartment of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)Department of Medical Oncology, IOV Istituto Oncologico VenetoSandro Pitigliani Medical Oncology Department, Nuovo Ospedale di PratoDepartment of Medical Oncology, AOU Ospedali Riuniti Di AnconaDepartment of Medical Oncology, AOU CagliariDepartment of Medical Oncology, Azienda Sanitaria Universitaria Integrata di UdineDepartment of Medical Oncology, AOU Careggi di FirenzeMedical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research CenterDepartment of Medical Oncology, IRCCS Policlinico San DonatoDepartment of Medical Oncology, Ospedale San GerardoDepartment of Medical Oncology, Fondazione PoliambulanzaDepartment of Medical Oncology, ASST della Valtellina e dell’Alto LarioDepartment of Medical Oncology, Ospedale di CremonaDepartment of Medical Oncology, Ospedale di Circolo e Fondazione MacchiDepartment of Medical Oncology, AOU San Luigi GonzagaDepartment of Medical Oncology, AOUI Verona Ospedale Policlinico ‘Giambattista Rossi’ di Borgo RomaDepartment of Medical Oncology, Ospedale Mater SalutisDepartment of Medical Oncology, AOU di ModenaDepartment of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCSDepartment of Medical Oncology, Ospedale degli infermi di RiminiDepartment of Medical Oncology, I.R.C.C.S. Istituto Tumori BariDepartment of Medical Oncology, Ospedale A. Perrino di BrindisiDepartment of Medical Oncology, Casa Sollievo della SofferenzaDepartment of Medical OncologyDepartment of Medical Oncology, Ospedale San DonatoDepartment of Medical Oncology, Azienda Ospedaliera “Ospedali Riuniti Marche Nord”Department of Medical Oncology, Fondazione Policlinico Universitario “A. Gemelli” - IRCCS, Università Cattolica del Sacro CuoreDepartment of Medical Oncology, A.O.U. Citta della Salute e della Scienza di TorinoDivision of Medical Oncology, Department of Precision Medicine, University of Campania ‘Luigi Vanvitelli’ - School of MedicineDepartment of Medical OncologyDepartment of Medical OncologyDepartment of Medical Oncology, Fondazione IRCCS Istituto Nazionale TumoriDepartment of Medical Oncology, Fondazione IRCCS Istituto Nazionale TumoriDepartment of Medical Oncology, Fondazione IRCCS Istituto Nazionale TumoriAbstract 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).http://link.springer.com/article/10.1186/s12885-019-5498-3Metastatic gastric cancerFirst lineMaintenanceRamucirumabClinical trial |