On January 2, 2024, the research groups of Professors Rui-hua Xu, Prof. Feng Wang and Prof. Zhiwei Zhou from Sun Yat-sen University Cancer Center published their research results titled ' Perioperative toripalimab and chemotherapy in locally advanced gastric or gastro-esophageal junction cancer: a randomized phase 2 trial ' in Nature Medicine. Through perioperative chemotherapy combined with immunotherapy, this study provides important evidence-based medicine for establishing new treatment strategy for locally advanced gastric cancer.
Patients with gastric and gastro-esophageal junction cancer are often diagnosed at an advanced stage, resulting in an overall poor prognosis. Compared to surgery alone, the addition of perioperative or adjuvant chemotherapy has improved survival outcomes of gastric cancer patients. Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1) in combination with chemotherapy have shown improved overall survival compared to chemotherapy alone for advanced gastric or gastro-esophageal junction adenocarcinoma. However, a randomized trial is urgently needed to compare the efficacy in locally advanced gastric cancer.
In this study, multidisciplinary teams of SYSUCC presented the results of a randomized phase 2 trial (NEOSUMMIT-01) to compare the efficacy of perioperative toripalimab plus chemotherapy versus chemotherapy alone in patients with cT3-4aN + M0 gastric or gastro-esophageal junction adenocarcinoma. After the study was successfully reported at the 2023 ASCO Annual Meeting, it has now been published in Natural Medicine
. The groundbreaking result lays a solid foundation for the development of future perioperative treatment models for gastric cancer, bringing new hope for longer survival of locally advanced gastric cancer patients.
Between 12 October 2019 and 27 June 2022 a total of 108 patients were randomly assigned to receive either toripalimab plus chemotherapy (n = 54) or chemotherapy alone (n = 54). The primary endpoint of the study was pathological complete response or near-complete response rate (tumor regression grade (TRG) 0/1). Secondary endpoints included pathological complete response of the primary tumor, margin-free resection (R0), recurrence-free survival, overall survival, treatment safety, et al.
The study results showed that patients in the toripalimab plus chemotherapy group achieved a higher proportion of TRG 0/1 than those in the chemotherapy group (44.4% versus 20.4%, P = 0.009). In addition, a higher pathological complete response rate (ypT0N0) was observed in the toripalimab plus chemotherapy group (22.2% versus 7.4%; P = 0.030). In a post hoc analysis, a greater proportion of patients in the toripalimab plus chemotherapy group achieved lower pathological tumor staging (ypT0–2) than in the chemotherapy group (46.3% versus 22.2%; P = 0.008).
In patients with intestinal or mixed-type histology, a higher proportion of patients in the toripalimab plus chemotherapy group achieved TRG 0/1 compared to the chemotherapy group, regardless of the PD-L1 expression or the MMR status.
The addition of preoperative toripalimab to chemotherapy did not increase the risk of perioperative adverse events, with similar rates of postoperative morbidity and 30-day mortality observed between the two treatment groups.
This study is the first reported randomized controlled clinical trial in the world to achieve the primary endpoint of perioperative immunotherapy combined with chemotherapy versus chemotherapy alone for locally advanced gastric cancer. It provides an effective treatment option for locally advanced gastric cancer, consolidating the leading position of the SYSUCC team in clinical research on gastric cancer immunotherapy.
Prof. Feng Wang
, Prof.Rui-hua Xu
and Prof. Zhiwei Zhou
from Sun Yat-sen University Cancer Center are the co-corresponding authors of this paper. Prof. Shuqiang Yuan, Dr. Runcong Nie, Prof. Ying Jin, Dr. Chengcai Liang and Prof. Yuanfang Li are the co-first authors of this paper.
Link to the original article: https://www.nature.com/articles/s41591-023-02721-w