An open label phase II study of total neoadjuvant therapy (TNT) consisting of FLOT with pembrolizumab and short radiation for patients with locally advanced gastroesophageal junction adenocarcinoma (EPOC2301)
Background: Durvalumab combined with fluorouracil, leucovorin, oxaliplatin, and docetaxel (D-FLOT) has demonstrated significant improvement in event-free survival (EFS) among patients with resectable gastric and gastroesophageal junction adenocarcinoma (GEJA) and is expected to become a new standard of care. Nevertheless, surgical resection remains requisite and is associated with substantial morbidity and deterioration in quality of life for GEJA. Given that D-FLOT achieves a pathological complete response in ∼20% of patients, intensification of total neoadjuvant therapy with short-course radiation (SRT) could further increase clinical CR (cCR) rates and facilitate non-operative management (NOM) in selected GEJA patients. Trial design: EPOC2301 is a single-arm, phase II study evaluating the efficacy and safety of pembrolizumab with FLOT plus SRT as total neoadjuvant therapy for resectable GEJA. Patients receive two cycles of FLOT and one dose of pembrolizumab, followed by 25 Gy radiotherapy, then two more cycles of FLOT and one dose of pembrolizumab. Response is assessed by computed tomography, positron emission tomography-computed tomography, endoscopy with bite-on-bite biopsy, and whole-genome circulating tumor DNA analysis. Patients achieving cCR or near-cCR continue NOM with pembrolizumab and FLOT, whereas those without adequate response undergo surgery followed by adjuvant pembrolizumab and FLOT. The primary endpoint is 3-year EFS.
Authors
- Hirokazu Shoji (ORCID: https://orcid.org/0000-0002-8922-5227)
- Kohei Shitara (ORCID: https://orcid.org/0000-0001-5196-3630)
- Kentaro Kato (ORCID: https://orcid.org/0000-0001-5820-3263)
- Mitsuko Suzuki (ORCID: https://orcid.org/0000-0002-2397-5551)
- Tetsuji Hayashi
- Masahiro Yura (ORCID: https://orcid.org/0000-0001-7102-9212)
- Tomonori Yano (ORCID: https://orcid.org/0000-0002-8030-1449)
- Shingo Sakashita (ORCID: https://orcid.org/0000-0003-1133-3313)
- Takashi Hashimoto (ORCID: https://orcid.org/0000-0002-0144-3255)
- Izuma Nakayama (ORCID: https://orcid.org/0000-0003-4987-1934)
- M. Wakabayashi
- T. Yoshino
- Tomohiro Kadota (ORCID: https://orcid.org/0000-0002-0408-3494)
- Tsutomu Fujita (ORCID: https://orcid.org/0000-0002-3651-6231)
- N Sakamoto (ORCID: https://orcid.org/0000-0003-0773-1343)
- Akihiro Sato (ORCID: https://orcid.org/0000-0002-0049-6718)
- Hiroyuki Daiko (ORCID: https://orcid.org/0000-0002-9562-2966)
- Tomonari Kinoshita (ORCID: https://orcid.org/0000-0001-5739-773X)
- Kazuma Sato
- M. Nakamura
Institutions
- National Cancer Center (US)
- National Cancer Center Hospital East (JP)
Publication Details
- Journal
- ESMO Gastrointestinal Oncology
- Published
- 2025-12-01
- DOI
- https://doi.org/10.1016/j.esmogo.2025.100267
- Primary Topic
- Esophageal Cancer Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Amgen
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Sanofi
- Taiho Pharmaceutical
- Miyarisan Pharmaceutical
- Myriad Genetics
- BeiGene
- Boehringer Ingelheim Japan
- Azərbaycan Milli Elmlər Akademiyası
- Moderna
- Natera
- Rakuten Medical
- Eisai
- Meiji Seika Pharma
- Astellas Pharma
- Shionogi
- Astellas Foundation for Research on Metabolic Disorders
- Ono Pharmaceutical
- Astellas Pharma Global Development
- Pfizer Japan
- Chugai Pharmaceutical
- MSD K.K.
- Daiichi Sankyo Europe