Abstract
Perioperative chemotherapy is the standard treatment for locally advanced gastric or gastro-esophageal junction cancer, and the addition of programmed cell death 1 (PD-1) inhibitor is under investigation. In this randomized, open-label, phase 2 study (NEOSUMMIT-01), patients with resectable gastric or gastro-esophageal junction cancer clinically staged as cT3-4aN + M0 were randomized (1:1) to receive either three preoperative and five postoperative 3-week cycles of SOX/XELOX (chemotherapy group, n = 54) or PD-1 inhibitor toripalimab plus SOX/XELOX, followed by toripalimab monotherapy for up to 6 months (toripalimab plus chemotherapy group, n = 54). The primary endpoint was pathological complete response or near-complete response rate (tumor regression grade (TRG) 0/1). The 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% (24 of 54, 95% confidence interval (CI): 30.9%–58.6%) versus 20.4% (11 of 54, 95% CI: 10.6%–33.5%)), and the risk difference of TRG 0/1 between toripalimab plus chemotherapy group and chemotherapy group was 22.7% (95% CI: 5.8%–39.6%; P = 0.009), meeting a prespecified endpoint. In addition, a higher pathological complete response rate (ypT0N0) was observed in the toripalimab plus chemotherapy group (22.2% (12 of 54, 95% CI: 12.0%–35.6%) versus 7.4% (4 of 54, 95% CI: 2.1%–17.9%); P = 0.030), and surgical morbidity (11.8% in the toripalimab plus chemotherapy group versus 13.5% in the chemotherapy group) and mortality (1.9% versus 0%), and treatment-related grade 3–4 adverse events (35.2% versus 29.6%) were comparable between the treatment groups. In conclusion, the addition of toripalimab to chemotherapy significantly increased the proportion of patients achieving TRG 0/1 compared to chemotherapy alone and showed a manageable safety profile. ClinicalTrials.gov registration: NCT04250948.
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Data availability
All requests for data will be reviewed by the leading clinical site, Sun Yat-Sen University Cancer Center, to verify whether the request is subject to any intellectual property or confidentiality obligations. Requests for access to the patient-level data from this study can be submitted via email to wangfeng@sysucc.org.cn with detailed proposals for approval and will be responded to in two weeks. A signed data access agreement with the sponsor is required before accessing shared data.
Code availability
No custom code was used for statistical analysis in this study.
Change history
08 January 2024
A Correction to this paper has been published: https://doi.org/10.1038/s41591-024-02800-6
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Acknowledgements
This study is sponsored by Shanghai Junshi Biosciences. We thank the patients who participated in this study and their families. We thank S. R. Seeruttun (Sun Yat-sen University Cancer Center) for assistance in writing and revising the contents of this work. This research was supported by the National Natural Science Foundation of China (81930065, 82173128, to R.H.X.), CAMS Innovation Fund for Medical Sciences (CIFMS) (2019-I2M-5-036, to R.H.X.), International Cooperation and Exchanges National Natural Science Foundation of China (82061160373, to F.W.), Science and Technology Program of Guangzhou (202206080011, to F.W.), the Fundamental Research Funds for the Central Universities,Sun Yat-sen University (84000-31620003, to F.W.), Young Talents Program of Sun Yat-sen University Cancer Center(YTP-SYSUCC-0018, to F.W.) and Guangdong Esophageal Cancer Institute Science and Technology Program (M02210, to S.Q.Y.). The funders played no role in the study’s design, conduct or reporting.
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R.-H.X., F.W., Z.-W.Z. and S.-Q.Y. conceived and designed the study. S.-Q.Y., R.-C.N., Y.J., C.-C.L., Y.-F.L., R.J., X.-W.S., Y.-B.C., W.-L.G., Z.-X.W., H.-B.Q., W.W., S.C., D.-S.Z., Y.-H.L., S.-Y.X., M.-Y.C., C.-Y.H., Q.-X.Y., Z.-M.L., Y.-X.G., Y.-M.C., J.-B.L., X.-W.T., J.-S.P., Z.-W.Z., F.W. and R.-H.X. conducted the provision of study materials and patients. R.-H.X., F.W., Z.-W.Z., S.-Q.Y. and R.-C.N. carried out data analysis and interpretation. All authors were involved in writing the manuscript and final approval.
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Yuan, SQ., Nie, RC., Jin, Y. et al. Perioperative toripalimab and chemotherapy in locally advanced gastric or gastro-esophageal junction cancer: a randomized phase 2 trial. Nat Med 30, 552–559 (2024). https://doi.org/10.1038/s41591-023-02721-w
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DOI: https://doi.org/10.1038/s41591-023-02721-w
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