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

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 & 19 others 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

Research output: Contribution to journalArticle

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).

Original languageEnglish
Article number283
JournalBMC Cancer
Volume19
Issue number1
DOIs
Publication statusPublished - Mar 29 2019

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Esophagogastric Junction
Paclitaxel
Stomach
Maintenance
Drug Therapy
Neoplasms
Stomach Neoplasms
Disease Progression
oxaliplatin
Platinum
Therapeutics
Disease-Free Survival
Quality of Life
ramucirumab
Treatment Failure
Drug Resistance
Health Status
Biomarkers
Safety
Survival

Keywords

  • Clinical trial
  • First line
  • Maintenance
  • Metastatic gastric cancer
  • Ramucirumab

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

Cite this

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. / Di Bartolomeo, Maria; Niger, Monica; Morano, Federica; Corallo, Salvatore; Antista, Maria; Tamberi, Stefano; Lonardi, Sara; Di Donato, Samantha; Berardi, Rossana; Scartozzi, Mario; Cardellino, Giovanni Gerardo; Di Costanzo, Francesco; Rimassa, Lorenza; Luporini, Alberto Gianluigi; Longarini, Raffaella; Zaniboni, Alberto; Bertolini, Alessandro; Tomasello, Gianluca; Pinotti, Graziella; Scagliotti, Giorgio; Tortora, Giampaolo; Bonetti, Andrea; Spallanzani, Andrea; Frassineti, Giovanni Luca; Tassinari, Davide; Giuliani, Francesco; Cinieri, Saverio; Maiello, Evaristo; Verusio, Claudio; Bracarda, Sergio; Catalano, Vincenzo; Basso, Michele; Ciuffreda, Libero; De Vita, Ferdinando; Parra, Hector Soto; Fornaro, Lorenzo; Caporale, Marta; De Braud, Filippo; Pietrantonio, Filippo.

In: BMC Cancer, Vol. 19, No. 1, 283, 29.03.2019.

Research output: Contribution to journalArticle

Di Bartolomeo, M, Niger, M, Morano, F, Corallo, S, Antista, M, Tamberi, S, Lonardi, S, Di Donato, S, Berardi, R, Scartozzi, M, Cardellino, GG, Di Costanzo, F, Rimassa, L, Luporini, AG, Longarini, R, Zaniboni, A, Bertolini, A, Tomasello, G, Pinotti, G, Scagliotti, G, Tortora, G, Bonetti, A, Spallanzani, A, Frassineti, GL, Tassinari, D, Giuliani, F, Cinieri, S, Maiello, E, Verusio, C, Bracarda, S, Catalano, V, Basso, M, Ciuffreda, L, De Vita, F, Parra, HS, Fornaro, L, Caporale, M, De Braud, F & Pietrantonio, F 2019, '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, vol. 19, no. 1, 283. https://doi.org/10.1186/s12885-019-5498-3
Di Bartolomeo, Maria ; Niger, Monica ; Morano, Federica ; Corallo, Salvatore ; Antista, Maria ; Tamberi, Stefano ; Lonardi, Sara ; Di Donato, Samantha ; Berardi, Rossana ; Scartozzi, Mario ; Cardellino, Giovanni Gerardo ; Di Costanzo, Francesco ; Rimassa, Lorenza ; Luporini, Alberto Gianluigi ; Longarini, Raffaella ; Zaniboni, Alberto ; Bertolini, Alessandro ; Tomasello, Gianluca ; Pinotti, Graziella ; Scagliotti, Giorgio ; Tortora, Giampaolo ; Bonetti, Andrea ; Spallanzani, Andrea ; Frassineti, Giovanni Luca ; Tassinari, Davide ; Giuliani, Francesco ; Cinieri, Saverio ; Maiello, Evaristo ; Verusio, Claudio ; Bracarda, Sergio ; Catalano, Vincenzo ; Basso, Michele ; Ciuffreda, Libero ; De Vita, Ferdinando ; Parra, Hector Soto ; Fornaro, Lorenzo ; Caporale, Marta ; De Braud, Filippo ; Pietrantonio, Filippo. / 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. In: BMC Cancer. 2019 ; Vol. 19, No. 1.
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TY - JOUR

T1 - 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

T2 - The ARMANI phase III trial

AU - Di Bartolomeo, Maria

AU - Niger, Monica

AU - Morano, Federica

AU - Corallo, Salvatore

AU - Antista, Maria

AU - Tamberi, Stefano

AU - Lonardi, Sara

AU - Di Donato, Samantha

AU - Berardi, Rossana

AU - Scartozzi, Mario

AU - Cardellino, Giovanni Gerardo

AU - Di Costanzo, Francesco

AU - Rimassa, Lorenza

AU - Luporini, Alberto Gianluigi

AU - Longarini, Raffaella

AU - Zaniboni, Alberto

AU - Bertolini, Alessandro

AU - Tomasello, Gianluca

AU - Pinotti, Graziella

AU - Scagliotti, Giorgio

AU - Tortora, Giampaolo

AU - Bonetti, Andrea

AU - Spallanzani, Andrea

AU - Frassineti, Giovanni Luca

AU - Tassinari, Davide

AU - Giuliani, Francesco

AU - Cinieri, Saverio

AU - Maiello, Evaristo

AU - Verusio, Claudio

AU - Bracarda, Sergio

AU - Catalano, Vincenzo

AU - Basso, Michele

AU - Ciuffreda, Libero

AU - De Vita, Ferdinando

AU - Parra, Hector Soto

AU - Fornaro, Lorenzo

AU - Caporale, Marta

AU - De Braud, Filippo

AU - Pietrantonio, Filippo

PY - 2019/3/29

Y1 - 2019/3/29

N2 - 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).

AB - 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).

KW - Clinical trial

KW - First line

KW - Maintenance

KW - Metastatic gastric cancer

KW - Ramucirumab

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U2 - 10.1186/s12885-019-5498-3

DO - 10.1186/s12885-019-5498-3

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JO - BMC Cancer

JF - BMC Cancer

SN - 1471-2407

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