Immunological impact of intraperitoneal and intravenous chemotherapy in ovarian cancer, translational analyses of the Phase 3 iPocc trial.
Journal
Gynecologic oncology
Journal Volume
191
Start Page
124
End Page
131
ISSN
1095-6859
Date Issued
2024-12
Author(s)
Ogasawara, Aiko
Matsushita, Hirokazu
Tan, Tuan Zea
Shintani, Daisuke
Ye, Jieru
Nagao, Shoji
Demachi-Okamura, Ayako
Muraoka, Daisuke
Kobayashi, Yukari
Kakimi, Kazuhiro
Yamaguchi, Rui
Matsuo, Keitaro
Yamamoto, Kouji
Fujiwara, Keiichi
Tan, David Shao Peng
Hasegawa, Kosei
Abstract
Background: The iPocc trial, a randomized, global phase 3 study that compared intraperitoneal (IP) and intravenous (IV) carboplatin with dose-dense paclitaxel chemotherapy in epithelial ovarian cancer (EOC) patients, demonstrated improved progression-free survival in patients who received IP chemotherapy. The present study aimed to investigate the role of preexisting tumor immunity in the clinical outcomes of patients receiving IP chemotherapy. Methods: This study involved analyzing patient data from the iPocc trial, selectively of those whose tumor specimens were preserved at the time of primary surgery. A total of 116 cases ((IP; n = 59), (IV; n = 57)) were subjected to microarray analysis. Single-sample gene set enrichment analyses were performed to evaluate the tumor immune microenvironment. Results: Patients with enhanced tumor infiltration of T cells, natural killer (NK) cells, and cytotoxic lymphocytes in the IP group had a longer overall survival (OS) than those in the IV group, but not in the group with low infiltration. IP therapy improved the OS of patients with high expression of immune-related genes such as CD8A and FOXP3. In patients' subdivided into “immune Hot” and “immune Cold” groups based on hierarchical clustering analysis using four parameters representing “Innate immunity,” “T cells,” “IFNG response” and “Inhibitory molecules,” IP therapy significantly improved prognosis in the “immune Hot” group, but not in the “immune Cold” group compared to that of IV therapy. Conclusions: IP chemotherapy enhances the survival rates of patients with EOC with an immune-Hot phenotype in the tumor microenvironment prior to treatment. (Japan Registry of Clinical Trials number, jRCTs031180141.)
Subjects
Immune response
Intraperitoneal chemotherapy
Ovarian cancer
SDGs
Type
journal article