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Sintilimab Plus Modified FOLFIRINOX in Metastatic or Recurrent Pancreatic Cancer: The Randomized Phase II CISPD3 Trial

  • Pancreatic Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) or modified FOLFIRINOX (mFFX) is the first-line standard of care for metastatic pancreatic adenocarcinoma; effective and safe treatment strategies are needed as survival remains poor. Sintilimab, a human immunoglobulin G4 monoclonal antibody for programmed cell death-1, has shown efficacy in various cancers. We evaluated the efficacy and safety of sintilimab with mFFX for metastatic/recurrent pancreatic ductal adenocarcinoma in China.

Patients and Methods

This was a single-center, randomized, controlled, open-label phase II study. Patients were assigned 1:1 to sintilimab + mFFX or mFFX (n = 55, each).

Results

In the intention-to-treat population, median overall survivals (primary endpoint) were similar in the sintilimab + mFFX and mFFX groups: 10.9 and 10.8 months, respectively [hazard ratio (HR) 1.07, 95% confidence interval (CI) 0.69–1.68]. The objective response rate was higher [50.0% (95% CI 34.6–65.4%) versus 23.9% (95% CI 11.1–36.7%)] in the sintilimab + mFFX group (P < 0.05). Median (HR, 95% CI) progression-free survival and disease control rates (95% CI) were also similar at 5.9 and 5.7 months (0.93, 0.62–1.40), and 84.1% (72.8–95.3%) and 71.7%, (58.2–85.3%), respectively. Incidences of grade ≥ 3 treatment-emergent adverse events were 84.9% (45/53) and 74.1% (40/54), and that of grade ≥ 3 immune-related adverse events were 5.7% (3/53) and 0 in each group, respectively.

Conclusions

The study did not meet its primary endpoint, no clear survival benefit was observed, and the benefit of sintilimab + mFFX for advanced pancreatic cancer was not supported; however, the findings suggest that using this regimen for pancreatic cancer is feasible, has an acceptable safety profile, and leads to an objective response rate of 50%.

Trial registration ClinicalTrials.Gov; NCT03977272

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Acknowledgement

The authors wish to thank Innovent Biologics (Suzhou) Co., Ltd. for providing the sintilimab.

Funding

This work was financially supported by the National Key Research and Development Program of China (No. 2019YFC1316000), the National Natural Science Foundation of China (No. 82071867, 81871925, 82172859), the Regional Innovation and Development Joint Fund National Natural Science Foundation of China (No. U20A20378), the Key Research Development Program of Zhejiang Province (No. 2019C03019, 2020C03117), the Fundamental Research Funds for the Central Universities and the Medical Science and Technology Program of Zhejiang Province (No. 2020382292), and the Fundamental Research Funds for the Zhejiang Provincial Universities (No. 2021XZZX031).

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Author notes

  1. Qihan Fu and Yiwen Chen shared co-first authorship.

Authors and Affiliations

  1. Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Yiwen Chen MD, Dabing Huang MS, Chengxiang Guo MD, Qi Zhang MD, Xiang Li PhD, Shunliang Gao MD, Risheng Que MD, Yan Shen MD, Jian Wu MD, PhD, Min Zhang MD, Xueli Bai MD, PhD & Tingbo Liang MD, PhD

  2. The Key Laboratory of Pancreatic Diseases of Zhejiang Province, Hangzhou, China

    Qihan Fu MD, Yiwen Chen MD, Dabing Huang MS, Chengxiang Guo MD, Qi Zhang MD, Xiang Li PhD, Xueli Bai MD, PhD & Tingbo Liang MD, PhD

  3. Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Qihan Fu MD & Xiaochen Zhang MD

  4. Cancer Center of Zhejiang University, Hangzhou, China

    Xueli Bai MD, PhD & Tingbo Liang MD, PhD

  5. Department of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Wenbo Xiao MD & Xing Xue MS

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Correspondence to Xueli Bai MD, PhD or Tingbo Liang MD, PhD.

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Fu, Q., Chen, Y., Huang, D. et al. Sintilimab Plus Modified FOLFIRINOX in Metastatic or Recurrent Pancreatic Cancer: The Randomized Phase II CISPD3 Trial. Ann Surg Oncol 30, 5071–5080 (2023). https://doi.org/10.1245/s10434-023-13383-w

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