New study by researchers at The Institute finds improved survival and potential for personalized treatment
A new study by researchers at The Institute demonstrates that combining immunotherapy with chemotherapy before surgery can improve outcomes for patients with locally advanced gastroesophageal adenocarcinoma (GEA).
The phase 2 clinical trial tested the addition of the PD-L1 inhibitor avelumab to a standard chemotherapy regimen (docetaxel, cisplatin, and fluorouracil, or DCF) for patients with locally advanced GEA. Led by Thierry Alcindor, MD, oncologist (formerly at The Institute, now at Dana Farber Cancer Center), and Lorenzo Ferri, MD, PhD, Director of Thoracic and Upper Gastrointestinal Surgery at the McGill University Health Centre, found this approach to be both safe and effective, with a two-year disease-free survival rate of 67.5%.
“Our findings mark an important step forward in pre-operative therapy for esophageal cancer and offer hope to patients facing this aggressive disease,” said Dr. Ferri, a Senior Scientist in the Cancer Research Program at The Institute and corresponding senior author of the study.
Key results and insights
The trial included 51 patients, with 50 proceeding to surgery. Among them, 14% achieved a complete pathological response (pCR), meaning no detectable cancer cells remained in the tissue samples taken during surgery — a strong indicator of better long-term outcomes.
The study also revealed new insights into treatment resistance. Analysis of immune cell populations showed that tumours from non-responding patients had increased levels of M2 tumour-associated macrophages (M2-TAMs), a type of immune cell linked to poor treatment outcomes. Further investigation revealed that M2-TAMs produced high levels of two proteins, MIF and CD86, which may suppress the immune response and reduce the effectiveness of treatment.
Next steps in research
“This was one of the first studies to explore immunotherapy combined with chemotherapy for esophageal cancer, and it provides the longest follow-up data on survival,” said Dr. Ferri. “Our next steps involve further investigating how M2 macrophages contribute to treatment resistance, and how immunotherapy can be enhanced to overcome this barrier.”
The study builds on over a decade of research advocating for neoadjuvant systemic therapy (treatment before surgery) for esophageal cancer. It follows a landmark paper published in the Annals of Oncology by Dr. Ferri and colleagues in 2012. Advances in immunotherapy have transformed treatment approaches, with checkpoint inhibitors like avelumab showing promise in boosting the immune system’s ability to target cancer cells. Combining chemotherapy with immunotherapy has emerged as a powerful strategy, aiming to improve survival rates and overcome resistance seen in traditional treatments. Dr. Ferri’s latest research reflects this progress, integrating these innovations to enhance outcomes for patients with aggressive gastroesophageal cancers.
Dr. Ferri’s work is supported by the Canadian Institutes of Health Research, the Canadian Cancer Society, the United States Department of Defense and the Montreal General Hospital (MGH) Foundation. The MGH Foundation is leading a new campaign, Together against Cancer, and through its Personalized, Precision Cancer Care Initiative, Dr. Ferri is developing a precision medicine research program to grow patient tumour replicas in the lab, allowing researchers to test various drugs and identify the most effective personalized treatments. His team has a five-year plan to refine the process, gain approval as a new standard of care for esophageal and gastric cancers, and expand its application to other cancer types across Canada. This approach aims to reduce exposure to ineffective and potentially toxic therapies while improving patient outcomes.
The research team thanks the Biobank platform at The Institute for their expertise in support of their work.
About the study
“Phase 2 trial of perioperative chemo-immunotherapy for gastro-esophageal adenocarcinoma: The role of M2 macrophage landscape in predicting response” by Thierry Alcindor, James Tanke, Pierre-Olivier Fiset, Sanjima Pal, Touhid Opu, Michael Strasser, Mehrnoush Dehghani, Nicholas Bertos, Dongmei Zuo, Carmen Mueller, Jonathan Cools-Lartigue, Marc Hickeson, Victoria Marcus, Sophie Camilleri-Broet, Alan Spatz, Gertruda Evaristo, Mina Farag, Giovanni Artho, Arielle Elkrief, Ramy Saleh, Swneke Bailey, Morag Park, Sui Huang, Veena Sangwan and Lorenzo Ferri published in Cell Reports Medicine.
DOI: 10.1016/j.xcrm.2025.102045
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