Ipilimumab or FOLFOX with Nivolumab and Trastuzumab in previously untreated HER2-positive locally advanced or metastatic EsophagoGastric Adenocarcinoma - the randomized phase 2 INTEGA trial (AIO STO 0217)
Abstract Background Esophagogastric adenocarcinoma (EGA) currently represents a main cause of cancer related death. Despite an intensified treatment for locally advanced or metastatic EGA with a doublet chemotherapy consisting of a platinum compound and a fluoropyrimidine in combination with trastuz...
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BMC
2020-06-01
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Online Access: | http://link.springer.com/article/10.1186/s12885-020-06958-3 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Joseph Tintelnot Eray Goekkurt Mascha Binder Peter Thuss-Patience Sylvie Lorenzen Jorge Riera Knorrenschild Albrecht Kretzschmar Thomas Ettrich Udo Lindig Lutz Jacobasch Daniel Pink Salah-Eddin Al-Batran Axel Hinke Susanna Hegewisch-Becker Sven Nilsson Carsten Bokemeyer Alexander Stein |
spellingShingle |
Joseph Tintelnot Eray Goekkurt Mascha Binder Peter Thuss-Patience Sylvie Lorenzen Jorge Riera Knorrenschild Albrecht Kretzschmar Thomas Ettrich Udo Lindig Lutz Jacobasch Daniel Pink Salah-Eddin Al-Batran Axel Hinke Susanna Hegewisch-Becker Sven Nilsson Carsten Bokemeyer Alexander Stein Ipilimumab or FOLFOX with Nivolumab and Trastuzumab in previously untreated HER2-positive locally advanced or metastatic EsophagoGastric Adenocarcinoma - the randomized phase 2 INTEGA trial (AIO STO 0217) BMC Cancer Esophagogastric adenocarcinoma HER2 Trastuzumab Nivolumab Ipilimumab FOLFOX |
author_facet |
Joseph Tintelnot Eray Goekkurt Mascha Binder Peter Thuss-Patience Sylvie Lorenzen Jorge Riera Knorrenschild Albrecht Kretzschmar Thomas Ettrich Udo Lindig Lutz Jacobasch Daniel Pink Salah-Eddin Al-Batran Axel Hinke Susanna Hegewisch-Becker Sven Nilsson Carsten Bokemeyer Alexander Stein |
author_sort |
Joseph Tintelnot |
title |
Ipilimumab or FOLFOX with Nivolumab and Trastuzumab in previously untreated HER2-positive locally advanced or metastatic EsophagoGastric Adenocarcinoma - the randomized phase 2 INTEGA trial (AIO STO 0217) |
title_short |
Ipilimumab or FOLFOX with Nivolumab and Trastuzumab in previously untreated HER2-positive locally advanced or metastatic EsophagoGastric Adenocarcinoma - the randomized phase 2 INTEGA trial (AIO STO 0217) |
title_full |
Ipilimumab or FOLFOX with Nivolumab and Trastuzumab in previously untreated HER2-positive locally advanced or metastatic EsophagoGastric Adenocarcinoma - the randomized phase 2 INTEGA trial (AIO STO 0217) |
title_fullStr |
Ipilimumab or FOLFOX with Nivolumab and Trastuzumab in previously untreated HER2-positive locally advanced or metastatic EsophagoGastric Adenocarcinoma - the randomized phase 2 INTEGA trial (AIO STO 0217) |
title_full_unstemmed |
Ipilimumab or FOLFOX with Nivolumab and Trastuzumab in previously untreated HER2-positive locally advanced or metastatic EsophagoGastric Adenocarcinoma - the randomized phase 2 INTEGA trial (AIO STO 0217) |
title_sort |
ipilimumab or folfox with nivolumab and trastuzumab in previously untreated her2-positive locally advanced or metastatic esophagogastric adenocarcinoma - the randomized phase 2 intega trial (aio sto 0217) |
publisher |
BMC |
series |
BMC Cancer |
issn |
1471-2407 |
publishDate |
2020-06-01 |
description |
Abstract Background Esophagogastric adenocarcinoma (EGA) currently represents a main cause of cancer related death. Despite an intensified treatment for locally advanced or metastatic EGA with a doublet chemotherapy consisting of a platinum compound and a fluoropyrimidine in combination with trastuzumab for HER2-positive disease or in selected cases with docetaxel, survival remains poor. Recently, immune-oncology based strategies relevantly improved the treatment of different solid tumors and showed some promise in late or later stage trials in EGA. Notably, the combination of immunotherapy with trastuzumab to enhance anti-tumor immunity through activation of innate and adaptive immunity was beneficial in preclinical studies or clinical studies in breast cancer. Methods The INTEGA study is an open-label, randomized, multicenter, exploratory phase II trial designed to assess clinical performance, safety and tolerability of ipilimumab or 5-FU/folinic acid and oxaliplatin (FOLFOX) in combination with nivolumab and trastuzumab in patients with previously untreated HER2-positive, locally advanced or metastatic EGA. The primary objective is to determine the clinical performance of ipilimumab or FOLFOX in combination with nivolumab and trastuzumab in terms of overall survival. Secondary objectives are safety and tolerability, efficacy in terms of progression-free survival and objective response rate and blood-based signatures (e.g. immune response or suppression of anti-HER2 resistance) that may correlate with treatment response. Discussion Recent evidence from the phase II NCT02954536 study (oxaliplatin, capecitabine, trastuzumab and pembrolizumab) suggests the clinical feasibility of combining chemotherapy, trastuzumab and checkpoint inhibition in EGA. However, evidence for a chemotherapy-free regimen is also mounting in HER2-positive disease (NCT02689284) i.e. margetuximab and Pembrolizumab. Both studies excelled with high overall response rates and manageable toxicities. The INTEGA study aims to comparatively assess these results and select a promising new 1st line regimen which then needs to be confirmed in a randomized phase III trial. Further, the translational part of the study might help to better stratify patients and tailor treatment of either arm. Trial registration NCT03409848 24.01.2018. |
topic |
Esophagogastric adenocarcinoma HER2 Trastuzumab Nivolumab Ipilimumab FOLFOX |
url |
http://link.springer.com/article/10.1186/s12885-020-06958-3 |
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doaj-8acdade897524e90ab934f07ed739b002020-11-25T03:20:38ZengBMCBMC Cancer1471-24072020-06-0120111010.1186/s12885-020-06958-3Ipilimumab or FOLFOX with Nivolumab and Trastuzumab in previously untreated HER2-positive locally advanced or metastatic EsophagoGastric Adenocarcinoma - the randomized phase 2 INTEGA trial (AIO STO 0217)Joseph Tintelnot0Eray Goekkurt1Mascha Binder2Peter Thuss-Patience3Sylvie Lorenzen4Jorge Riera Knorrenschild5Albrecht Kretzschmar6Thomas Ettrich7Udo Lindig8Lutz Jacobasch9Daniel Pink10Salah-Eddin Al-Batran11Axel Hinke12Susanna Hegewisch-Becker13Sven Nilsson14Carsten Bokemeyer15Alexander Stein16Department of Internal Medicine II (Oncology Center), University Medical Center Hamburg-Eppendorf, Hubertus Wald Tumorzentrum/UCCHDepartment of Internal Medicine II (Oncology Center), University Medical Center Hamburg-Eppendorf, Hubertus Wald Tumorzentrum/UCCHUniversity Hospital Halle-WittenbergCharité, University Medicine BerlinRechts der Isar Hospital, Technical University of MunichUniversity Hospital of Giessen and MarburgMVZ Mitte, Practice for Hematology and OncologyUniversity Hospital UlmUniversity Hospital JenaPractice of Hematology and OncologyHelios Clinic Bad Saarow, Bad Saarow, Germany and University Medicine GreifswaldKrankenhaus Nordwest, UCT University Cancer CenterCCRCHematology-Oncology Practice Hamburg (HOPE)Department of Internal Medicine II (Oncology Center), University Medical Center Hamburg-Eppendorf, Hubertus Wald Tumorzentrum/UCCHDepartment of Internal Medicine II (Oncology Center), University Medical Center Hamburg-Eppendorf, Hubertus Wald Tumorzentrum/UCCHDepartment of Internal Medicine II (Oncology Center), University Medical Center Hamburg-Eppendorf, Hubertus Wald Tumorzentrum/UCCHAbstract Background Esophagogastric adenocarcinoma (EGA) currently represents a main cause of cancer related death. Despite an intensified treatment for locally advanced or metastatic EGA with a doublet chemotherapy consisting of a platinum compound and a fluoropyrimidine in combination with trastuzumab for HER2-positive disease or in selected cases with docetaxel, survival remains poor. Recently, immune-oncology based strategies relevantly improved the treatment of different solid tumors and showed some promise in late or later stage trials in EGA. Notably, the combination of immunotherapy with trastuzumab to enhance anti-tumor immunity through activation of innate and adaptive immunity was beneficial in preclinical studies or clinical studies in breast cancer. Methods The INTEGA study is an open-label, randomized, multicenter, exploratory phase II trial designed to assess clinical performance, safety and tolerability of ipilimumab or 5-FU/folinic acid and oxaliplatin (FOLFOX) in combination with nivolumab and trastuzumab in patients with previously untreated HER2-positive, locally advanced or metastatic EGA. The primary objective is to determine the clinical performance of ipilimumab or FOLFOX in combination with nivolumab and trastuzumab in terms of overall survival. Secondary objectives are safety and tolerability, efficacy in terms of progression-free survival and objective response rate and blood-based signatures (e.g. immune response or suppression of anti-HER2 resistance) that may correlate with treatment response. Discussion Recent evidence from the phase II NCT02954536 study (oxaliplatin, capecitabine, trastuzumab and pembrolizumab) suggests the clinical feasibility of combining chemotherapy, trastuzumab and checkpoint inhibition in EGA. However, evidence for a chemotherapy-free regimen is also mounting in HER2-positive disease (NCT02689284) i.e. margetuximab and Pembrolizumab. Both studies excelled with high overall response rates and manageable toxicities. The INTEGA study aims to comparatively assess these results and select a promising new 1st line regimen which then needs to be confirmed in a randomized phase III trial. Further, the translational part of the study might help to better stratify patients and tailor treatment of either arm. Trial registration NCT03409848 24.01.2018.http://link.springer.com/article/10.1186/s12885-020-06958-3Esophagogastric adenocarcinomaHER2TrastuzumabNivolumabIpilimumabFOLFOX |