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

被引：16

作者：

Raimondi, A. ^{[1
]}

Lonardi, S. ^{[2
]}

Murgioni, S. ^{[3
]}

Cardellino, G. G. ^{[4
]}

Tamberi, S. ^{[5
]}

Strippoli, A. ^{[6
]}

Palermo, F. ^{[1
]}

De Manzoni, G. ^{[7
]}

Bencivenga, M. ^{[7
]}

Bittoni, A. ^{[8
]}

Chiodoni, C. ^{[9
]}

Lorenzini, D. ^{[10
]}

Todoerti, K. ^{[10
]}

Manca, P. ^{[1
]}

Sangaletti, S. ^{[9
]}

Prisciandaro, M. ^{[1
]}

Randon, G. ^{[1
]}

Nichetti, F. ^{[1
]}

Bergamo, F. ^{[3
]}

Brich, S. ^{[10
]}

Belfiore, A. ^{[10
]}

Bertolotti, A. ^{[10
]}

Stetco, D. ^{[10
]}

Guidi, A. ^{[10
]}

Torelli, T. ^{[10
]}

Vingiani, A. ^{[10
]}

Joshi, R. P. ^{[11
]}

Khoshdeli, M. ^{[11
]}

Beaubier, N. ^{[11
]}

Stumpe, M. C. ^{[11
]}

Nappo, F. ^{[3
]}

Leone, A. G. ^{[1
]}

Pircher, C. C. ^{[1
]}

Leoncini, G. ^{[10
]}

Sabella, G. ^{[10
]}

Farulla, L. Airo' ^{[12
]}

Alessi, A. ^{[12
]}

Morano, F. ^{[1
]}

Martinetti, A. ^{[1
]}

Niger, M. ^{[1
]}

Fassan, M. ^{[13
]}

Di Maio, M. ^{[14
]}

Kaneva, K. ^{[11
]}

Milione, M. ^{[10
]}

Nimeiri, H. ^{[11
]}

Sposito, C. ^{[15
,16
]}

Agnelli, L. ^{[1
,10
]}

Mazzaferro, V. ^{[15
,16
]}

Di Bartolomeo, M. ^{[1
]}

Pietrantonio, F. ^{[1
]}

机构：

[1] Ist Nazl Tumori IRCCS Milan, Dept Med Oncol, Milan, Italy

[2] Veneto Inst Oncol IOV IRCCS, Med Oncol 3, Padua, Italy

[3] Veneto Inst Oncol IOV IRCCS, Med Oncol 1, Padua, Italy

[4] Presidio Osped Santa Maria Misericordia ASUFC, Dept Oncol, Udine, Italy

[5] Ravenna Hosp, AUSL Romagna, Oncol Unit, Ravenna, Italy

[6] Fdn Policlin Univ A Gemelli IRCCS, Med Oncol Unit, Rome, Italy

[7] Azienda Osped Univ Integrata Verona Borgo Trento, Dept Surg, I-37100 Verona, Italy

[8] IRCCS, Ist Romagnolo Studio Tumori IRST Dino Amadori, Meldola, Italy

[9] Fdn IRCCS Ist Nazl Tumori, Dept Expt Oncol, Mol Immunol Unit, Milan, Italy

[10] Fdn IRCCS Ist Nazl Tumori, Dept Diagnost Innovat, Milan, Italy

[11] Tempus, Chicago, IL USA

[12] Ist Nazl Tumori IRCCS Milan, Div Nucl Med, Milan, Italy

[13] Univ Padua, Sch Med & Surg, Padua, Italy

[14] Univ Turin, Le Molinette Hosp, Dept Radiol, I-10126 Turin, Italy

[15] Univ Milan, Dept Oncol, Milan, Italy

[16] Ist Nazl Tumori IRCCS Milan, GI Surg, Milan, Italy

来源：

ANNALS OF ONCOLOGY | 2025年 / 36卷 / 03期

关键词：

gastric cancer; microsatellite instability; immunotherapy; non-operative management; ADJUVANT CHEMOTHERAPY; MISMATCH REPAIR; CANCER; EFFICACY; SURGERY; IMMUNOTHERAPY; BENEFIT; SAFETY; TRIAL; S-1;

D O I：

10.1016/j.annonc.2024.11.016

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 months median follow-up, one patient had local regrowth and underwent salvage surgery; 12-month gastrectomy-free survival was 64.2%. Conclusions: The INFINITY study provided promising activity results of a chemo-free T300/D combination regimen as preoperative treatment in mismatch repair deficient/MSI gastric/gastroesophageal junction adenocarcinoma and the first available feasibility results of a non-operative management strategy in this disease setting, worthy of further validation in larger cohorts.

引用

页码：285 / 296

页数：12

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