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TENERGY: multicenter phase II study of Atezolizumab monotherapy following definitive Chemoradiotherapy with 5-FU plus Cisplatin in patients with unresectable locally advanced esophageal squamous cell carcinoma
BACKGROUND: The standard treatment for patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC) is definitive chemoradiotherapy (CRT) using 5-FU plus cisplatin. However, complete response (CR) rates are low at 11–25%, resulting in 9–10 months of median overall survival (...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168951/ https://www.ncbi.nlm.nih.gov/pubmed/32312286 http://dx.doi.org/10.1186/s12885-020-06716-5 |
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author | Bando, Hideaki Kotani, Daisuke Tsushima, Takahiro Hara, Hiroki Kadowaki, Shigenori Kato, Ken Chin, Keisho Yamaguchi, Kensei Kageyama, Shun-ichiro Hojo, Hidehiro Nakamura, Masaki Tachibana, Hidenobu Wakabayashi, Masashi Fukutani, Miki Togashi, Yosuke Fuse, Nozomu Nishikawa, Hiroyoshi Kojima, Takashi |
author_facet | Bando, Hideaki Kotani, Daisuke Tsushima, Takahiro Hara, Hiroki Kadowaki, Shigenori Kato, Ken Chin, Keisho Yamaguchi, Kensei Kageyama, Shun-ichiro Hojo, Hidehiro Nakamura, Masaki Tachibana, Hidenobu Wakabayashi, Masashi Fukutani, Miki Togashi, Yosuke Fuse, Nozomu Nishikawa, Hiroyoshi Kojima, Takashi |
author_sort | Bando, Hideaki |
collection | PubMed |
description | BACKGROUND: The standard treatment for patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC) is definitive chemoradiotherapy (CRT) using 5-FU plus cisplatin. However, complete response (CR) rates are low at 11–25%, resulting in 9–10 months of median overall survival (OS). An improved therapeutic efficacy by combining immunotherapy with radiation has been reported in patients with locally advanced non-small cell lung cancer. The results using ESCC cell lines suggest sequential treatment with anti-PD-L1 agents soon after completion of CRT is the most effective combination. METHODS: TENERGY trial is a multicenter, phase II, proof-of-concept study to assess the efficacy and safety of atezolizumab following definitive CRT in patients with locally advanced ESCC. The main inclusion criteria are unresectable locally advanced ESCC without distant metastasis, completion of 60 Gy of radiation plus two concomitant cycles of chemotherapy (cisplatin 70 mg/m(2) on day 1 and 5-FU 700 mg/m(2) on days 1–4, every 28 days), and adequate organ function. Within 6 weeks after CRT, participants will start taking 1200 mg of atezolizumab every three weeks and continue until 12 months or disease progression. The primary endpoint is the confirmed CR rate by the investigator’s assessment. Secondary endpoints include overall response rate, progression-free survival (PFS), OS, adverse events, and confirmed CR rate by central assessment. We will enroll 50 patients (40 with primary locally advanced ESCC and 10 with postoperative locoregionally recurrent ESCC). We will obtain biopsies from the primary site and will collect blood at 3 time points (before CRT, after CRT, and four weeks after the start of atezolizumab) for an exploratory biomarker study. We will analyze the phenotype of immune-competent cells, neoantigens, tumor mutational burden, PD-L1 status, and Human Leukocyte Antigen haplotyping. DISCUSSION: The synergistic efficacies of the sequential combination of CRT and atezolizumab should improve the CR rate, resulting in survival improvement for patients with unresectable locally advanced ESCC. Because CRT is a standard treatment option for patients with early stage to locally advanced ESCC, the sequential combination of CRT and atezolizumab has the potential to change the standard ESCC treatments. TRIAL REGISTRATION: UMIN000034373, 10/04/2018 and EPOC1802. |
format | Online Article Text |
id | pubmed-7168951 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-71689512020-04-23 TENERGY: multicenter phase II study of Atezolizumab monotherapy following definitive Chemoradiotherapy with 5-FU plus Cisplatin in patients with unresectable locally advanced esophageal squamous cell carcinoma Bando, Hideaki Kotani, Daisuke Tsushima, Takahiro Hara, Hiroki Kadowaki, Shigenori Kato, Ken Chin, Keisho Yamaguchi, Kensei Kageyama, Shun-ichiro Hojo, Hidehiro Nakamura, Masaki Tachibana, Hidenobu Wakabayashi, Masashi Fukutani, Miki Togashi, Yosuke Fuse, Nozomu Nishikawa, Hiroyoshi Kojima, Takashi BMC Cancer Study Protocol BACKGROUND: The standard treatment for patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC) is definitive chemoradiotherapy (CRT) using 5-FU plus cisplatin. However, complete response (CR) rates are low at 11–25%, resulting in 9–10 months of median overall survival (OS). An improved therapeutic efficacy by combining immunotherapy with radiation has been reported in patients with locally advanced non-small cell lung cancer. The results using ESCC cell lines suggest sequential treatment with anti-PD-L1 agents soon after completion of CRT is the most effective combination. METHODS: TENERGY trial is a multicenter, phase II, proof-of-concept study to assess the efficacy and safety of atezolizumab following definitive CRT in patients with locally advanced ESCC. The main inclusion criteria are unresectable locally advanced ESCC without distant metastasis, completion of 60 Gy of radiation plus two concomitant cycles of chemotherapy (cisplatin 70 mg/m(2) on day 1 and 5-FU 700 mg/m(2) on days 1–4, every 28 days), and adequate organ function. Within 6 weeks after CRT, participants will start taking 1200 mg of atezolizumab every three weeks and continue until 12 months or disease progression. The primary endpoint is the confirmed CR rate by the investigator’s assessment. Secondary endpoints include overall response rate, progression-free survival (PFS), OS, adverse events, and confirmed CR rate by central assessment. We will enroll 50 patients (40 with primary locally advanced ESCC and 10 with postoperative locoregionally recurrent ESCC). We will obtain biopsies from the primary site and will collect blood at 3 time points (before CRT, after CRT, and four weeks after the start of atezolizumab) for an exploratory biomarker study. We will analyze the phenotype of immune-competent cells, neoantigens, tumor mutational burden, PD-L1 status, and Human Leukocyte Antigen haplotyping. DISCUSSION: The synergistic efficacies of the sequential combination of CRT and atezolizumab should improve the CR rate, resulting in survival improvement for patients with unresectable locally advanced ESCC. Because CRT is a standard treatment option for patients with early stage to locally advanced ESCC, the sequential combination of CRT and atezolizumab has the potential to change the standard ESCC treatments. TRIAL REGISTRATION: UMIN000034373, 10/04/2018 and EPOC1802. BioMed Central 2020-04-20 /pmc/articles/PMC7168951/ /pubmed/32312286 http://dx.doi.org/10.1186/s12885-020-06716-5 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Study Protocol Bando, Hideaki Kotani, Daisuke Tsushima, Takahiro Hara, Hiroki Kadowaki, Shigenori Kato, Ken Chin, Keisho Yamaguchi, Kensei Kageyama, Shun-ichiro Hojo, Hidehiro Nakamura, Masaki Tachibana, Hidenobu Wakabayashi, Masashi Fukutani, Miki Togashi, Yosuke Fuse, Nozomu Nishikawa, Hiroyoshi Kojima, Takashi TENERGY: multicenter phase II study of Atezolizumab monotherapy following definitive Chemoradiotherapy with 5-FU plus Cisplatin in patients with unresectable locally advanced esophageal squamous cell carcinoma |
title | TENERGY: multicenter phase II study of Atezolizumab monotherapy following definitive Chemoradiotherapy with 5-FU plus Cisplatin in patients with unresectable locally advanced esophageal squamous cell carcinoma |
title_full | TENERGY: multicenter phase II study of Atezolizumab monotherapy following definitive Chemoradiotherapy with 5-FU plus Cisplatin in patients with unresectable locally advanced esophageal squamous cell carcinoma |
title_fullStr | TENERGY: multicenter phase II study of Atezolizumab monotherapy following definitive Chemoradiotherapy with 5-FU plus Cisplatin in patients with unresectable locally advanced esophageal squamous cell carcinoma |
title_full_unstemmed | TENERGY: multicenter phase II study of Atezolizumab monotherapy following definitive Chemoradiotherapy with 5-FU plus Cisplatin in patients with unresectable locally advanced esophageal squamous cell carcinoma |
title_short | TENERGY: multicenter phase II study of Atezolizumab monotherapy following definitive Chemoradiotherapy with 5-FU plus Cisplatin in patients with unresectable locally advanced esophageal squamous cell carcinoma |
title_sort | tenergy: multicenter phase ii study of atezolizumab monotherapy following definitive chemoradiotherapy with 5-fu plus cisplatin in patients with unresectable locally advanced esophageal squamous cell carcinoma |
topic | Study Protocol |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168951/ https://www.ncbi.nlm.nih.gov/pubmed/32312286 http://dx.doi.org/10.1186/s12885-020-06716-5 |
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