曲美木单抗和度伐利尤单抗作为微卫星高度不稳定的可切除胃癌或胃食管交界腺癌患者的新辅助或非手术治疗策略：GONO的INFINITY研究

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.

作者信息

Raimondi A, Lonardi S, Murgioni S, Cardellino G G, Tamberi S, Strippoli A, Palermo F, De Manzoni G, Bencivenga M, Bittoni A, Chiodoni C, Lorenzini D, Todoerti K, Manca P, Sangaletti S, Prisciandaro M, Randon G, Nichetti F, Bergamo F, Brich S, Belfiore A, Bertolotti A, Stetco D, Guidi A, Torelli T, Vingiani A, Joshi R P, Khoshdeli M, Beaubier N, Stumpe M C, Nappo F, Leone A G, Pircher C C, Leoncini G, Sabella G, Airo' Farulla L, Alessi A, Morano F, Martinetti A, Niger M, Fassan M, Di Maio M, Kaneva K, Milione M, Nimeiri H, Sposito C, Agnelli L, Mazzaferro V, Di Bartolomeo M, Pietrantonio F

机构信息

Department of Medical Oncology, Istituto Nazionale Tumori IRCCS Milan, Milan, USA.

Medical Oncology 3, Veneto Institute of Oncology IOV - IRCCS, Padua, USA.

出版信息

Ann Oncol. 2025 Mar;36(3):285-296. doi: 10.1016/j.annonc.2024.11.016. Epub 2024 Dec 3.

DOI:10.1016/j.annonc.2024.11.016

PMID:39637944

Abstract

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.

摘要

背景

在可切除的胃/胃食管交界腺癌中，微卫星高度不稳定（MSI-H）可改善生存，但化疗获益有限。免疫疗法可能无需化疗或手术。

患者与方法

INFINITY是一项多中心、多队列的II期试验（NCT04817826），在队列1中研究替雷利珠单抗+度伐利尤单抗（T300/D）作为错配修复缺陷/MSI-H、可切除胃/胃食管交界腺癌新辅助治疗的活性和安全性。主要终点是病理完全缓解（pCR）率；次要终点：无进展生存期（PFS）、总生存期（OS）、生活质量和转化分析。在队列2中，探索T300/D作为实现临床完全缓解（cCR）患者的确定性治疗的活性和安全性。主要终点是2年cCR率，次要终点是PFS、OS、生活质量、无胃切除术生存期和转化分析。

结果

在队列1中，招募了18例患者，15例可评估。pCR和主要病理反应-pCR分别为60%和80%。由于T4肿瘤的pCR率为17%，该亚组患者被排除在队列2的入组之外。在中位随访28.1个月时，24个月的胃癌特异性PFS和OS率分别为85%和92%。在队列2中，招募了18例患者，17例可评估，13例有cCR并开始非手术治疗。在中位随访11.5个月时，1例患者出现局部复发并接受挽救性手术；12个月的无胃切除术生存期为64.2%。