Perioperative PD-1 antibody toripalimab plus SOX or XELOX chemotherapy versus SOX or XELOX alone for locally advanced gastric or gastro-oesophageal junction cancer: Results from a prospective, randomized, open-label, phase II trial.
Shuqiang Yuan, Run‐Cong Nie, Ying Jin, Chengcai Liang, Rui Jian, Yuanfang Li, Haibo Qiu, Wei Wang, Shi Chen, Dongsheng Zhang, Chunyu Huang, Yihong Ling, Qiuxia Yang, Zixian Wang, Wen‐Long Guan, Ying-Bo Chen, Xiaowei Sun, Zhiwei Zhou, Feng Wang, Rui‐Hua Xu
Abstract
4001 Background: The combination of PD-1 antibody and chemotherapy was shown to be effective in advanced gastric or gastro-oesophageal junction (GEJ) cancer, but has not yet been investigated in the context of locally advanced patients. In this study, we conducted a prospective, randomized, open-label phase II trial to evaluate the effectiveness of adding PD-1 antibody to perioperative chemotherapy in patients with locally advanced resectable gastric or GEJ cancer. Methods: In this randomized, open-label, phase II study, patients with resectable gastric or GEJ cancer clinically staged as cT3-4a N+M0 were randomized (1:1) to three preoperative and five postoperative 3-week cycles of SOX/XELOX (C arm) or PD-1 antibody toripalimab plus SOX/XELOX, followed by toripalimab monotherapy for 6 months (C+T arm). The primary endpoint was pathological complete regression/moderate regression rate (TRG 0/1). The secondary endpoints were pathological complete response (pCR), R0 resection rate, recurrence-free survival, event-free survival, objective response rate, disease control rate, overall survival and treatment safety. The study had been completed enrollment, and here, we analyzed the primary endpoint. Mantel-Haenszel test was used to test the difference of pathological regression between the two arms. The trial was registered at ClinicalTrials.gov, identifier: NCT04250948. Results: Between Oct 2019 and June 2022, 108 patients (C+T arm, n=54; C arm, n=54) were enrolled and assessed using intention-to-treat analysis. Patients in the toripalimab plus chemotherapy arm achieved higher proportion of TRG 0/1 than those in the chemotherapy arm (44.4% [24/54, 95% CI: 30.9%-58.6%] vs 20.4% [11/54, 95% CI: 10.6%-33.5%]; P=0.009). A higher pCR rate was observed in the C+T arm (24.1% [13/54, 95% CI:13.5%-37.6%] vs 9.3% [5/54, 95% CI: 3.1%-20.3%]; P=0.039). Preoperative therapies (3 cycles) were completed in 96.3% of patients and postoperative cycles (>3 cycles) in 81.5%, with no significant differences observed between these two arms. A higher proportion of downstaging was observed in the C+T arm (ypT0-2: 46.3% vs 22.2% [P=0.002]; ypstage 0-1: 38.9% vs 16.7% [P=0.024]). Surgical morbidity (11.8% in the C+T arm vs 13.5% in the C arm) and mortality (1.9% vs 0%) and treatment-related grade 3-4 adverse events (27.8% vs 25.9%) were comparable between the arms. Conclusions: Perioperative PD-1 antibody toripalimab plus chemotherapy demonstrated a significantly improved pathological regression and might be a promising option for patients with locally advanced resectable gastric or GEJ cancer. Clinical trial information: NCT04250948 .