1435P - Immunomodulatory effects and improved survival of PG2 plus preoperative chemoradiotherapy in patients with locally advanced esophageal cancer

Background

Esophageal squamous cell carcinoma (ESCC) treatment remains challenging due to its high recurrence rates and discouraging survival outcomes. Astragalus Polysaccharides (PG2, PhytoHealth Corporation, Taiwan, ROC), as a drug therapy for cancer-related fatigue relief, has the ability to modulate macrophage polarization and synergistically anti-cancer effect. PG2 combined with neoadjuvant chemoradiotherapy might be a novel therapeutic strategy in patients with ESCC.

Methods

The prospective, multicenter, open-label, and randomized trial included patients with stage IIb to IIIb resectable locally advanced ESCC who would undergo concurrent chemoradiotherapy (CCRT) followed by surgery. Eligible patients were randomized to receive either CCRT combined with PG2 or CCRT alone. This study aimed to identify differences in survival, objective response rate (ORR), and major pathologic response (MPR) rate between two arms. The Immunomodulatory effects of PG2 were also explored.

Results

Thirty-eight ESCC patients were enrolled. CCRT combined with PG2 resulted in significantly superior overall survival (OS) compared to CCRT alone [HR 0.32; 95% CI, 0.1-0.96; P=0.042]. The ORR in CCRT-PG2 arm was 85.0%, higher than that in CCRT alone arm was 62.5%, and progressive disease made surgery unfeasible for 5% of cases in CCRT-PG2 arm, while 25.0% in CCRT alone arm. Primary tumor MPR rate was achieved by 100.0% in CCRT-PG2 Arm and 80.0% in CCRT alone arm, respectively. CCRT-PG2 arm exhibited a consistent and significant decline in blood regulatory T cell proportions, and the suppressions of the serum levels of proinflammatory cytokines (IL-12, IL-1b, and IL-6), immune- suppressive cytokines (IL-10 and IL-4), and angiogenic growth factors (VEGF and MCP-1) were also observed in CCRT-PG2 arm, with a significant difference compared to the CCRT alone arm. PG2 also conferred an immunomodulatory effect by reducing CCRT-induced polarization of tumor-associated macrophages from M1 to M2.

Conclusions

PG2 combined with preoperative CCRT in advanced esophageal cancer has shown promising improvements in OS and modulation of the immune microenvironment.

Clinical trial identification

NCT03611712 (PH-CP028/PH-CP028-1).

Editorial acknowledgement

Legal entity responsible for the study

MacKay Memorial Hospital, Tri-Service General Hospital, Far-Eastern Memorial Hospital, Taipei Medical University - Shuang-Ho Hospital, PhytoHealth Corporation.

Funding

PhytoHealth Corporation, Taiwan.

Disclosure

All authors have declared no conflicts of interest.