Neoadjuvant cadonilimab plus FLOT chemotherapy in locally advanced gastric/gastroesophageal junction adenocarcinoma: A multicenter, phase 2 study.

IF 12.8 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Med Pub Date : 2024-11-08 DOI:10.1016/j.medj.2024.10.008

Bo Long, Huinian Zhou, Zeyuan Yu, Junmin Zhu, Hanteng Yang, Zeping Huang, Dengwen Wei, Shigong Chen, Xiaojun Yang, Xiaoning Zhao, Wenjuan Zhang, Hong Yan, Xiaoying Guan, Long Li, Gengyuan Zhang, Hongwei Yu, Shengfu Che, Zhongti Gao, Xiangyan Jiang, Changjiang Luo, Jie Mao, Da Zhao, Yumin Li, Zebin Jiang, Zuoyi Jiao

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Abstract

Background: Treatment with cadonilimab and chemotherapy has shown promise as a first-line treatment for gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. However, its application in neoadjuvant settings has not yet been documented.

Methods: This multicenter, phase 2 trial (ChiCTR2200066893) was conducted at four hospitals across China. Treatment-naive patients with locally advanced G/GEJ adenocarcinoma (cT3/4, N+, M0) and who were human epidermal growth factor receptor 2 negative received 3-cycle or 4-cycle neoadjuvant treatment of cadonilimab plus FLOT (5-fluorouracil, leucovorin, oxaliplatin, and docetaxel) chemotherapy, followed by gastrectomy and 4-cycle adjuvant FLOT chemotherapy. The primary endpoint was the pathological complete response (pCR) rate. Secondary endpoints included major pathological response (MPR), overall response rate (ORR), disease control rate (DCR), R0 resection rate, downstaging rate, and safety.

Findings: Between December 23, 2022, and December 15, 2023, 32 of 38 patients completed the scheduled treatment, achieving an R0 resection rate of 100% (32/32). The pCR rate was 21.1% (8/38, 90% confidence interval [CI]: 9.7-32.4), and the MPR rate was 44.7% (17/38, 90% CI: 30.9-58.5). Radiological evaluations were available for 28 of 38 patients by blinded independent central review. The ORR was 60.7% (17/28, 90% CI: 44.7-76.7), and the DCR was 100.0% (28/28, 90% CI: 100.0-100.0). Tumor downstaging occurred in 71.9% of patients (23/32), with consistent efficacy across all populations observed in the subgroup analysis. Grade 3 adverse events occurred in 31.6% of patients without severe safety issues.

Conclusions: Neoadjuvant cadonilimab plus FLOT chemotherapy treatment exhibits promising efficacy with manageable toxicities in locally advanced G/GEJ adenocarcinoma, providing preliminary evidence for further investigation.

Funding: This study was funded by Akeso Biopharma.

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局部晚期胃/胃食管交界腺癌新辅助卡多尼单抗加FLOT化疗：一项多中心2期研究。

背景：卡多尼单抗和化疗有望成为胃或胃食管交界处腺癌（G/GEJ）的一线治疗方法。然而，该疗法在新辅助治疗中的应用尚未得到证实：这项多中心 2 期试验（ChiCTR2200066893）在全国四家医院进行。局部晚期G/GEJ腺癌（cT3/4，N+，M0）且人类表皮生长因子受体2阴性的患者接受3个周期或4个周期的卡多尼单抗+FLOT（5-氟尿嘧啶、亮菌素、奥沙利铂和多西他赛）新辅助化疗，然后进行胃切除术和4个周期的FLOT辅助化疗。主要终点是病理完全反应率（pCR）。次要终点包括主要病理反应（MPR）、总反应率（ORR）、疾病控制率（DCR）、R0切除率、降期率和安全性：2022年12月23日至2023年12月15日期间，38名患者中有32人完成了预定治疗，R0切除率达到100%（32/32）。pCR率为21.1%（8/38，90%置信区间[CI]：9.7-32.4），MPR率为44.7%（17/38，90%置信区间[CI]：30.9-58.5）。通过盲法独立中央审查，38 名患者中有 28 人获得了放射学评估。ORR为60.7%（17/28，90% CI：44.7-76.7），DCR为100.0%（28/28，90% CI：100.0-100.0）。71.9%的患者（23/32）进行了肿瘤分期，在亚组分析中观察到所有人群的疗效一致。31.6%的患者发生了3级不良反应，没有出现严重的安全性问题：新辅助卡多尼单抗加FLOT化疗对局部晚期G/GEJ腺癌具有良好的疗效和可控的毒性，为进一步研究提供了初步证据：本研究由Akeso生物制药公司资助。

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来源期刊

Med MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

17.70

自引率

0.60%

发文量

102

期刊介绍： Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically. Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.