Tremelimumab and durvalumab as neoadjuvant or non-operative management strategy of patients with microsatellite instability-high resectable gastric or gastroesophageal junction adenocarcinoma: the INFINITY study by GONO

作者：A. Raimondi, Sara Lonardi, Sabina Murgioni, Giovanni Gerardo Cardellino, Stefano Tamberi, Antonia Strippoli, Federica Palermo, Giovanni De Manzoni, Maria Bencivenga, Alessandro Bittoni, Claudia Chiodoni, Daniele Lorenzini, Katia Todoerti, Paolo Manca, S. Sangaletti, Michele Prisciandaro, Giovanni Randon, F. Nichetti, Francesca Bergamo, Silvia Brich, Antonino Belfiore, Alessia Bertolotti, Daiana Stetco, Alessandro Guidi, Tommaso Torelli, A. Vingiani, Rohan P. Joshi, Mina Khoshdeli, Nike T. Beaubier, Martin C. Stumpe, Floriana Nappo, Alberto Giovanni Leone, C.C. Pircher, Giuseppe Leoncini, Giovanna Sabella, Lighea Simona Airò Farulla, Alessandra Alessi, Federica Morano, A. Martinetti, Monica Niger, M. Fassan, Massimo Di Maïo, Kristiyana Kaneva, M. Milione, Halla Sayed Nimeiri, Carlo Sposito, Luca Agnelli, Vincenzo Mazzaferro, Maria Di Bartolomeo, Filippo Pietrantonio · 发表于：Annals of Oncology · 年份：2024 · DOI：10.1016/j.annonc.2024.11.016 · 被引用次数：95 · 研究领域：Gastric Cancer Management and Outcomes、Esophageal Cancer Research and Treatment、Cancer Immunotherapy and Biomarkers

BACKGROUND: In resectable gastric/gastroesophageal junction adenocarcinoma, microsatellite instability-high (MSI-H) confers improved survival, but limited benefit from chemotherapy. Immunotherapy may eliminate the need for chemotherapy or surgery. PATIENTS AND METHODS: INFINITY is a multicenter, multicohort phase II trial (NCT04817826) investigating in cohort 1 the activity and safety of tremelimumab + durvalumab (T300/D) as neoadjuvant treatment of mismatch repair deficient/MSI-H, resectable gastric/gastroesophageal junction adenocarcinoma. Primary endpoint was pathologic complete response (pCR) rate; Secondary endpoints: progression-free survival (PFS), overall survival (OS), quality of life, and translational analyses. In cohort 2, the activity and safety of T300/D was explored as definitive treatment in patients achieving clinical complete response (cCR). Primary endpoint was 2-year cCR rate, and secondary endpoints were PFS, OS, quality of life, gastrectomy-free survival and translational analyses. RESULTS: In cohort 1, 18 patients were recruited and 15 evaluable. pCR and major pathologic response-pCR were 60% and 80%, respectively. Since pCR rate in T4 tumors was 17%, this subgroup of patients was excluded from enrollment in cohort 2. At 28.1 months median follow-up, 24-month gastric cancer-specific PFS and OS rates were 85% and 92%, respectively. In cohort 2, 18 patients were enrolled and 17 assessable, and 13 had cCR and started non-operative management. At 11.5 month...