Abstract 5266: Deciphering the systemic immune effects of abemaciclib in recurrent metastatic breast cancer: A multicenter, prospective study
Authors: Yukiko Fukui, Kosuke Kawaguchi, Yurina Maeshima, Yuri Fujimoto, Hiroshi Ishiguro, Kazuhiko Yamagami, Sachiko Takahara, Hirofumi Suwa, Masae Torii, Shigenori Nagai, Yasuaki Sagara, Wakako Tsuji, Hiroyasu Yamashiro, Takeshi Kotake, Shinji Fukuda, Kuniaki Saito, Yasuko Yamamoto, Masako Kataoka, Yuki Himoto, Atsushi Yonezawa, Yuki Nakamura, Wei Li, Sunao Tanaka, Satoshi Morita, Masahiro Takada, Masakazu Toi
Journal: Cancer Research (2024)

Abstract Background: Abemaciclib, a CDK4/6 inhibitor, stands as a cornerstone for managing hormone receptor-positive, HER2-negative advanced or metastatic recurrent breast cancer. It is known to modulate the tumor immune microenvironment, enhancing anti-tumor responses. Yet, its systemic immunological impact remains to be elucidated. This investigation aims to delineate the influence of abemaciclib on both the gut microbiota and the systemic immune landscape in patients with breast cancer. Methods: A multicenter, prospective clinical trial was conducted involving 40 patients with hormone receptor-positive, HER2-negative advanced or metastatic recurrent breast cancer, scheduled for abemaciclib therapy. The trial's primary objectives were to evaluate the duration of treatment efficacy and the severity of gastrointestinal toxicity. Secondary objectives included assessing the interplay between circulating immune profiles, gut microbiota, and clinical outcomes. Patient samples, including peripheral blood mononuclear cells (PBMCs) for single-cell RNA sequencing and stool for 16S rRNA gene analysis, were collected at baseline and after 90 days of treatment initiation. Results: This interim report presents findings from 39 patients. We examined 75 PBMC samples and 78 stool samples. Preliminary analysis indicated that abemaciclib precipitated an upregulation of cytokines pivotal for anti-tumor immunity, notably IL-7 and IP-10, alongside an activation of circulating innate immune cells such as CD4-positive T cells and dendritic cells. Concurrently, gut microbiota analysis revealed a post-treatment reduction in alpha diversity, with notable shifts in microbial populations implicated in innate immune activation. Discussion: This study presents novel insights into the systemic immunomodulatory effects of abemaciclib. Our results suggest that abemaciclib's therapeutic efficacy may partially derive from its ability to alter the circulating immune profile and gut microbiota. These findings could pave the way for innovative immunotherapeutic approaches, integrating gut microbiome considerations into the treatment of hormone receptor-positive, HER2-negative breast cancer. Citation Format: Yukiko Fukui, Kosuke Kawaguchi, Yurina Maeshima, Yuri Fujimoto, Hiroshi Ishiguro, Kazuhiko Yamagami, Sachiko Takahara, Hirofumi Suwa, Masae Torii, Shigenori Nagai, Yasuaki Sagara, Wakako Tsuji, Hiroyasu Yamashiro, Takeshi Kotake, Shinji Fukuda, Kuniaki Saito, Yasuko Yamamoto, Masako Kataoka, Yuki Himoto, Atsushi Yonezawa, Yuki Nakamura, Wei Li, Sunao Tanaka, Satoshi Morita, Masahiro Takada, Masakazu Toi. Deciphering the systemic immune effects of abemaciclib in recurrent metastatic breast cancer: A multicenter, prospective study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5266.