Tremelimumab和durvalumab作为微卫星不稳定性高可切除的胃或胃食管结腺癌患者的新辅助或非手术治疗策略：GONO的INFINITY研究

IF 56.7 1区医学 Q1 ONCOLOGY

Annals of Oncology Pub Date : 2024-12-03 DOI:10.1016/j.annonc.2024.11.016

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

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引用次数: 0

摘要

背景：在可切除的胃/胃食管连接处腺癌（GAC/GEJAC）中，微卫星不稳定性（MSI-H）可以改善生存，但化疗的益处有限。免疫疗法可以消除化疗或手术的需要。患者和方法：INFINITY是一项多中心、多队列II期试验（NCT04817826），在队列1中研究tremelimumab+durvalumab （T300/D）作为dMMR/MSI-H、可切除GAC/GEJAC的新辅助治疗的活性和安全性。主要终点为病理完全缓解（pCR）率；次要终点：无进展生存期（PFS）、总生存期（OS）、生活质量（QoL）和转化分析。在队列2中，研究人员探索了T300/D作为达到临床完全缓解（cCR）的患者的最终治疗方法的活性和安全性。主要终点是2年cCR率，次要终点：PFS、OS、QoL、无胃切除术生存期（GFS）和转化分析。结果：在队列1中，18名患者被招募，15名可评估。pCR和主要完全病理反应分别为60%和80%。由于T4肿瘤的pCR率为17%，因此该亚组患者被排除在队列2的入组中。在中位随访28.1个月时，24个月gc特异性PFS和OS率分别为85%和92%。在队列2中，18例患者入组，17例可评估，13例有cCR并开始非手术治疗（NOM）。中位随访11.5个月时，1例患者局部再生并行补救性手术，12个月GFS为64.2%。结论：INFINITY研究提供了无化疗T300/D联合方案作为dMMR/MSI GAC/GEJAC术前治疗的有希望的活性结果，以及NOM策略在这种疾病环境下的第一个可用可行性结果，值得在更大的队列中进一步验证。

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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.

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.

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来源期刊

Annals of Oncology 医学-肿瘤学

CiteScore

63.90

自引率

1.00%

发文量

3712

审稿时长

2-3 weeks

期刊介绍： Annals of Oncology, the official journal of the European Society for Medical Oncology and the Japanese Society of Medical Oncology, offers rapid and efficient peer-reviewed publications on innovative cancer treatments and translational research in oncology and precision medicine. The journal primarily focuses on areas such as systemic anticancer therapy, with a specific emphasis on molecular targeted agents and new immune therapies. We also welcome randomized trials, including negative results, as well as top-level guidelines. Additionally, we encourage submissions in emerging fields that are crucial to personalized medicine, such as molecular pathology, bioinformatics, modern statistics, and biotechnologies. Manuscripts related to radiotherapy, surgery, and pediatrics will be considered if they demonstrate a clear interaction with any of the aforementioned fields or if they present groundbreaking findings. Our international editorial board comprises renowned experts who are leaders in their respective fields. Through Annals of Oncology, we strive to provide the most effective communication on the dynamic and ever-evolving global oncology landscape.