Hypofractionated radiotherapy plus PD-1 antibody and SOX chemotherapy as second-line therapy in metastatic pancreatic cancer: a single-arm, phase II clinical trial

Cancer Immunol Immunother. 2024 Aug 6;73(10):201. doi: 10.1007/s00262-024-03744-z.

Abstract

Purpose: To assess the efficacy and safety of concurrent hypofractionated radiotherapy plus anti-PD-1 antibody and SOX chemotherapy in the treatment of metastatic pancreatic cancer (mPC) after failure of first-line chemotherapy.

Methods: Patients with pathologically confirmed mPC who failed standard first-line chemotherapy were enrolled. The patients were treated with a regimen of hypofractionated radiotherapy, SOX chemotherapy, and immune checkpoint inhibitors at our institution. We collected the patients' clinical information and outcome measurements. The median progression-free survival (mPFS) was the primary endpoint of the study, followed by disease control rate (DCR), objective response rate (ORR), median overall survival (mOS) and safety. Exploratory analyses included biomarkers related to the benefits.

Results: Between February 24, 2021, and August 30, 2023, twenty-five patients were enrolled in the study, and twenty-three patients who received at least one dose of the study agent had objective efficacy evaluation. The mPFS was 5.48 months, the mOS was 6.57 months, and the DCR and ORR were 69.5% and 30.4%, respectively. Among the seven patients who achieved a PR, the median duration of the response was 7.41 months. On-treatment decreased serum CA19-9 levels were associated with better overall survival. Besides, pretreatment inflammatory markers were associated with tumor response and survival.

Conclusions: Clinically meaningful antitumor activity and favorable safety profiles were demonstrated after treatment with these combination therapies in patients with refractory mPC. On-treatment decreased serum CA19-9 levels and pretreatment inflammatory markers platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), lactate dehydrogenase (LDH) might be biomarkers related to clinical benefits.

Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=130211 , identifier: ChiCTR2100049799, date of registration: 2021-08-09.

Keywords: Hypofractionated radiotherapy; Immune checkpoint inhibitors; Metastatic pancreatic cancer; SOX chemotherapy; Second-line therapy.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Chemoradiotherapy / methods
  • Female
  • Gemcitabine
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Oxonic Acid / administration & dosage
  • Oxonic Acid / therapeutic use
  • Pancreatic Neoplasms* / drug therapy
  • Pancreatic Neoplasms* / pathology
  • Pancreatic Neoplasms* / radiotherapy
  • Pancreatic Neoplasms* / therapy
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Radiation Dose Hypofractionation*
  • Tegafur / administration & dosage
  • Tegafur / therapeutic use

Substances

  • Programmed Cell Death 1 Receptor
  • Immune Checkpoint Inhibitors
  • Oxonic Acid
  • PDCD1 protein, human
  • Tegafur
  • Gemcitabine