Neoadjuvant PD-(L)1 blockade with or without chemotherapy versus chemotherapy alone in mismatch repair-deficient, potentially resectable stage III-IVA gastric cancer patients: a single-center retrospective study

World J Surg Oncol. 2024 Nov 26;22(1):313. doi: 10.1186/s12957-024-03601-4.

Abstract

Background: Currently, PD-(L)1 blockade-based neoadjuvant treatment has shown promising outcomes in patients with potentially resectable gastric cancer. In this real-world study, we aimed to retrospectively observe the efficacy including tumor response and event-free survival (EFS), and safety of PD-(L)1 blockade-based neoadjuvant treatment versus chemotherapy alone in potentially resectable gastric cancer patients with microsatellite instability-high (MSI-H) or mismatch-repair deficient (dMMR) status.

Methods: We retrospectively collected the clinical data of patients with potentially resectable gastric cancer and MSI-H/dMMR status who received neoadjuvant treatment followed by D2 gastrectomy at the Affiliated Hospital of Qingdao University from January 2019 to June 2023. The outcomes of interest mainly included overall complete response (CR) rates, radiographical and pathological tumor response, treatment-related adverse events (TRAEs), and EFS.

Results: In total, 30 patients were included in the analysis; 23 patients received neoadjuvant PD-(L)1 blockade plus chemotherapy or PD-(L)1 blockade monotherapy, and seven patients received neoadjuvant chemotherapy. In the PD-(L)1 blockade-based treatment group, 7 of 23 patients (30.4%, 95% CI 0.141-0.530) achieved pathological CR (pCR), while three patients with radiographical CR did not undergo surgery. In contrast, 1 of 7 (14.3%) patients in the neoadjuvant chemotherapy group achieved pCR. The overall CR rate was 43.5% (10 of 23, 95% CI 0.239-0.651) in the PD-(L)1 blockade-based treatment group and 14.3% (1 of 7, 95% CI 0.026-0.513) in the chemotherapy group. The neoadjuvant PD-(L)1 blockade-based treatment regimen was mild and well tolerated. By the latest follow-up, median EFS time was not reached in both cohorts.

Conclusion: In potentially resectable gastric cancer patients with MSI-H/dMMR status, PD-(L)1 blockade-based neoadjuvant treatment regimen provided promising clinical benefits and was well tolerated.

Keywords: Gastric cancer; Immune checkpoint blockade; Mismatch repair deficiency; Neoadjuvant treatment; PD-L1.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • B7-H1 Antigen* / antagonists & inhibitors
  • Chemotherapy, Adjuvant / methods
  • DNA Mismatch Repair
  • Female
  • Follow-Up Studies
  • Gastrectomy* / methods
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Male
  • Microsatellite Instability
  • Middle Aged
  • Neoadjuvant Therapy* / methods
  • Neoplasm Staging*
  • Prognosis
  • Retrospective Studies
  • Stomach Neoplasms* / drug therapy
  • Stomach Neoplasms* / pathology
  • Stomach Neoplasms* / surgery
  • Survival Rate

Substances

  • CD274 protein, human
  • B7-H1 Antigen
  • Immune Checkpoint Inhibitors