Phase II Adjuvant Cancer-specific Vaccine Therapy for Esophageal Cancer Patients Curatively Resected After Preoperative Therapy With Pathologically Positive Nodes; Possible Significance of Tumor Immune Microenvironment in its Clinical Effects. Issue 1 (January 2022)

• Record Type: Journal Article
• Authors: Yasuda, Takushi; Nishiki, Kohei; Hiraki, Yoko; Kato, Hiroaki; Iwama, Mitsuru; Shiraishi, Osamu; Yasuda, Atsushi; Shinkai, Masayuki; Kimura, Yutaka; Sukegawa, Yasushi; Chiba, Yasutaka; Imano, Motohiro; Takeda, Kazuyoshi; Satou, Takao; Shiozaki, Hitoshi; Nakamura, Yusuke
• Is Part Of: Annals of surgery. Volume 275:Issue 1(2022)
• Publication Date: 2022-01
• Subjects: adjuvant peptide vaccine -- cytotoxic T lymphocyte -- esophageal cancer -- programmed cell death-ligand 1 -- squamous cell carcinoma -- tumor microenvironment; Surgery -- Periodicals; 617.005
• DOI: 10.1097/SLA.0000000000003880
• Languages: English
• ISSNs: 0003-4932

Abstract

Abstract : Objectives: To elucidate the efficacy of adjuvant vaccine monotherapy using 3 Human Leukocyte Antigen (HLA)-A * 24-restricted tumor-specific peptide antigens for ESCC, upregulated lung cancer 10, cell division cycle associated 1, and KH domain-containing protein overexpressed in cancer 1. Summary of Background Data: ESCC patients with pathologically positive nodes (pN(+)) have a high risk for postoperative recurrence, despite curative resection after preoperative therapy. Subclinical micrometastases are an appropriate target for cancer vaccine. Methods: This is a non-randomized prospective phase II clinical trial (UMIN000003557). ESCC patients curatively resected after preoperative therapy with pN(+) were allocated into the control and vaccine groups (CG and VG) according to the HLA-A status. One mg each of three epitope peptides was postoperatively injected 10 times weekly followed by 10 times biweekly to the VG. The primary and secondary endpoints were relapse-free survival (RFS) and esophageal cancer-specific survival (ECSS), respectively. Results: Thirty were in the CG and 33 in the VG. No significant difference was observed in RFS between the CG and VG (5-year RFS: 32.5% vs 45.3%), but the recurrence rate significantly decreased with the number of peptides which induced antigen-specific cytotoxic T lymphocytes. The VG showed a significantly higher 5-year ECSS than the CG (60.0% vs 32.4%, P = 0.045) and this difference was more prominent in patients with CD8 + and programmed death-ligand 1 double negative tumor (68.0% vs 17.7%, P = 0.010). Conclusions: Our cancer peptide vaccine might improve the survival of ESCC patients, which is warranted to be verified in the phase III randomized controlled study. Abstract : Supplemental Digital Content is available in the text