Phase I/II Trial of Perioperative Avelumab in Combination With Chemoradiation in the Treatment of Stage II/III Resectable Esophageal and Gastroesophageal Junction Cancer

Sep 24, 2026

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Standard treatment for stage II/III esophageal or gastroesophageal junction (E/GEJ) cancer uses neoadjuvant chemoradiation, surgical resection, and immunotherapy. This trial assessed whether adding perioperative avelumab to standard care could improve safety and efficacy. Patients with resectable E/GEJ cancers received avelumab with chemoradiation and adjuvant avelumab after resection, with safety and pCR as phase I and II primary endpoints. Twenty-two patients were enrolled; resection rates and pCR were reported, and grade 3+ events were limited.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages9

Reading Time23 min

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Introduction

Methods

Results

Conclusions

Journal of Surgical Oncology RESEARCH ARTICLE Phase I/II Trial of Perioperative Avelumab in Combination With Chemoradiation in the Treatment of Stage II/III Resectable Esophageal and Gastroesophageal Junction Cancer Nataliya V. Uboha1,2 | Mustafa M. Basree3 | Jens C. Eickhoff4 | Dustin A. Deming1,2 | Kristina Matkowskyj5,6 | James Maloney5,7 | Daniel McCarthy7 | Malcolm DeCamp7 | Noelle LoConte1,2 | Philip B. Emmerich1 | Sean Kraus1 | Monica A. Patel1,2 | Jeremy D. Kratz1,2,5,8 | Sam J. Lubner1,2 | Newton Hurst3 | Michael F. Bassetti3 1Division of Hematology, Medical Oncology and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA | 2Carbone Cancer Center, Madison, Wisconsin, USA | 3Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA | 4Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA | 5William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin, USA | 6Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA | 7Division of Cardiothoracic Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA | 8Center for Human Genomics and Precision Medicine, University of Wisconsin, Madison, Wisconsin, USA Correspondence: Nataliya V. Uboha ([nvuboha@medicine.wisc.edu](nvuboha@medicine.wisc.edu)) Received: 18 April 2024 | Revised: 18 November 2024 | Accepted: 18 December 2024 Funding: This study was supported by University of Wisconsin Carbone Cancer Center Support Grant P30 CA014520 and by the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945) . Keywords: chemoradiation | esophageal cancer | gastroesophageal adenocarcinoma | immunotherapy ABSTRACT Background and Objectives: Standard treatment of patients with stage II/III esophageal or gastroesophageal junction (E/GEJ) cancer involves neoadjuvant chemoradiation (nCRT), resection, and immunotherapy. Our trial evaluated the addition of perioperative avelumab to standard treatments. Methods: Patients with resectable E/GEJ cancers received avelumab with nCRT and adjuvant avelumab after resection. Primary endpoints for phase I and II portions were safety and pathologic complete response (pCR) rate, respectively. Secondary endpoints included recurrence‐free survival (RFS), surgical complication prevalence, and R0 resection rate. Results: Twenty‐two patients enrolled in the study. Median follow‐up during data cutoff was 23.9 months. There were no dose‐ limiting toxicities during the run‐in phase. Nineteen patients (86.4%) underwent resection with R0 resection rate of 78.9% and with pCR rate of 26% . Most common treatment‐related adverse events (TRAE) were cytopenias from chemoradiation. Aside from one grade ≥ 3 avelumab‐related hypersensitivity, no grade ≥ 3 avelumab TRAEs were seen. Median RFS was not reached, and 1‐year RFS and overall survival were 71% and 81%, respectively. The study was terminated before full planned accrual due to standard practice change based on the CheckMate 577 trial. Conclusions: The addition of perioperative avelumab to nCRT was tolerable and demonstrated promising outcomes. | Institution where the study was performed: University of Wisconsin‐Madison, USA. | | --- | | This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
© 2025 The Author(s) . Journal of Surgical Oncology published by Wiley Periodicals LLC. | Journal of Surgical Oncology, 2025; 131:1293–1301 1293 of 1472 [https://doi.org/10.1002/jso.28070](https://doi.org/10.1002/jso.28070) 1 | Introduction Esophag

FAQs

What treatment strategy did the trial evaluate for stage II/III resectable E/GEJ cancer?

The study evaluated perioperative avelumab added to standard neoadjuvant chemoradiation, followed by surgical resection and adjuvant avelumab after resection.

What were the primary endpoints in the phase I and phase II parts of the trial?

Phase I primary endpoint was safety, while phase II primary endpoint was the pathologic complete response (pCR) rate.

What were the key findings on tolerability and efficacy signals?

The addition of perioperative avelumab was tolerable, with no dose-limiting toxicities in the run-in phase and limited grade 3+ avelumab-related adverse events. The study reported resection outcomes and a pCR rate, with median recurrence-free survival not reached at data cutoff.

Sep 24, 2026

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