Efficacy and safety of sintilimab plus XELOX as a neoadjuvant regimen in patients with locally advanced gastric cancer: A single-arm, open-label, phase II trial

Honghai Guo; Ping'an Ding; Chenyu Sun; Peigang Yang; Yuan Tian; Yang Liu; Scott Lowe; Rachel Bentley; Yaru Li; Zhidong Zhang; Dong Wang; Yong Li; Qun Zhao

doi:10.3389/fonc.2022.927781

Efficacy and safety of sintilimab plus XELOX as a neoadjuvant regimen in patients with locally advanced gastric cancer: A single-arm, open-label, phase II trial

Front Oncol. 2022 Aug 26:12:927781. doi: 10.3389/fonc.2022.927781. eCollection 2022.

Authors

Honghai Guo¹, Ping'an Ding¹, Chenyu Sun², Peigang Yang¹, Yuan Tian¹, Yang Liu¹, Scott Lowe³, Rachel Bentley³, Yaru Li^{4

5}, Zhidong Zhang¹, Dong Wang¹, Yong Li¹, Qun Zhao¹

Affiliations

¹ The Third Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
² Internal Medicine, AMITA Health Saint Joseph Hospital Chicago, Chicago, Illinois, United States.
³ College of Osteopathic Medicine, Kansas City University, Kansas City, MO, United States.
⁴ Internal Medicine, Swedish Hospital, Chicago, IL, United States.
⁵ College of Osteopathic Medicine, Des Moines University, Des Moines, IA, United States.

Abstract

Background: Neoadjuvant chemotherapies have been widely recommended in patients with locally advanced gastric cancer (LAGC). However, the evidence of combining neoadjuvant chemotherapy with anti-programmed death 1 (anti-PD-1) antibody therapy for patients with LAGC is lacking. Thus, we conducted a single-arm phase II trial to evaluate the efficacy and safety of the anti-PD-1 antibody sintilimab plus XELOX regimen (capecitabine plus oxaliplatin) in patients with LAGC.

Methods: Patients with LAGC (cT3-4 N+ M0, CY0, P0) were enrolled and received four preoperative cycles of sintilimab (200 mg, IV, Q21d) plus XELOX (oxaliplatin 130 mg/m², IV, d1 with capecitabine 1,000 mg/m², bid, d1-d14, Q21d) therapy. The primary endpoint was the pathological complete response (pCR) rate. This clinical trial was registered at Chictr.org.cn (trial number: ChiCTR2000030414).

Results: Thirty patients were enrolled from March 2020 to July 2021, with a median age of 62 years (range, 30-72), and 18 (60.0%) were men. There were 19 (63.3%) patients with PD-L1 CPS ≥1.The pCR rate was 33.3% [95% confidence interval (CI), 17.3%-52.8%], and the major pathologic response (MPR) rate was 63.3% (95% CI, 43.9%-80.1%). All the patients underwent R0 resection. The objective response rate (ORR) and the disease control rate (DCR) were 70.0% (95% CI, 50.6%-85.3%) and 100% (95% CI, 88.4%-100%), respectively. Downstaging of the overall TNM stage was observed in 22 (73.3%) patients. The pCR rate in patients with PD-L1 CPS ≥1 and patients with PD-L1 CPS <1 was 42.1% vs. 18.2% (P = 0.246), whereas the MPR rate was 78.9% vs. 36.4% (P = 0.047). The potential immune-related adverse events (irAEs) were hypothyroidism (3.3%), pneumonia (10.0%), and dermatitis (6.7%). Grade3 common treatment-related adverse events (TRAEs) were ALT increase (3.3%), AST increase (3.3%), and dermatitis (3.3%) during the neoadjuvant therapy. There were no severe complications or death related to the surgery.

Conclusion: Sintilimab plus XELOX as neoadjuvant therapy showed an encouraging pCR rate, MPR rate, and manageable safety. This combination of regimens might provide a new option for patients with LAGC. Clinical Trial Registration: Chictr.org.cn, identifier ChiCTR2000030414.

Keywords: immunotherapy; locally advanced gastric cancer; neoadjuvant regimen; phase II trial; sintilimab.