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
N1 - M1 - 283
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
U2 - 10.1186/s12885-019-5498-3
DO - 10.1186/s12885-019-5498-3
M3 - Article
VL - 19
JO - BMC Cancer
JF - BMC Cancer
SN - 1471-2407
IS - 1
M1 - 283
ER -