Abstract PO2-06-04: Prospective study on eribulin efficacy in advanced and metastatic breast cancer: changes in TGF-β compared to other standard chemotherapy agents (KBCSG-TR 2018, POTENTIAL)

Abstract Introduction Eribulin (E) has been demonstrated to improve overall survival (OS) compared to standard chemotherapies in pivotal phase III clinical trials (studies 301 and 305), although there was no difference in progression-free survival. These findings suggest that E might have a mechanism for OS improvement different from the common anti-tumor effect. Several studies reported that E inhibits epithelial-mesenchymal transition and the suppression of TGF-β plays a central role. Data on the relationship between the E-induced serial change in TGF-β and the improvement in OS remains insufficient. Therefore, we conducted this prospective observational study of patients treated with E while undergoing sequential TGF-β testing. This study also enrolled patients who received chemotherapy other than E as a control. Methods Patients with HER2-negative recurrent/metastatic breast cancer (MBC) were prospectively enrolled from 23 breast cancer centers in Japan, if they had not previously used E, had received two or fewer prior chemotherapy regimens, and were scheduled to start either E, capecitabine, S-1 or paclitaxel (± bevacizumab) between September 2020 and February 2022. The target sample sizes were 150 and 50 patients scheduled to receive E (Cohort E) and other drugs (Cohort Others), respectively. We collected blood samples for TGF-β testing at baseline, at two or three weeks (week 2/3), and at four or five weeks (week 4/5) from the beginning. The observation period was until February 2023. The primary endpoint was to evaluate the relationship between changes in TGF-β and clinical response, including OS and time to treatment failure (TTF). Results A total of 202 of the 203 enrolled patients were included in the analysis (1 patient declined consent). The median age was 60.0 (interquartile range, 52.0-69.0) years and ECOG performance status was 0 or 1 in all patients. Among 152 patients in Cohort E and 50 patients in Cohort Others, 37 patients (24.3%) and 12 patients (24.0%) had hormonal receptor-negative breast cancer, and 29 patients (19.1%) and 30 patients (60.0%) had no prior chemotherapy for MBC, respectively. Visceral metastasis totaled 115 (75.7%) in Cohort E and 46 (92.0%) in Cohort Others. In OS analysis of 199 patients, the median OS was 24.5 months (95% CI, 17.3-NA) for no prior chemotherapy, and 17.7 months for one or two prior chemotherapy (median follow-up 14.5 months). In Cohort E and Cohort Others, 139 and 45 patients, respectively, had paired samples for TGF-β testing at baseline and week 2/3. The proportion of patients with a percent change at week 2/3 from baseline in TGF-β (ΔTGF-β) of less than zero (decreased TGF-β) was 46.8% in Cohort E and 33.3% in Cohort Others, indicating a 13.4% (-2.6% – 29.5%) higher trend in Cohort E. Based on the time-dependent receiver operating characteristic (ROC) curves at 6 months for TTF, the threshold of ΔTGF-β was determined to be 27%. For the low ΔTGF-β group ( 27%) and the high ΔTGF-β group (≥27%), OS rates at median follow-up (14.5 months) were 70.6% and 54.3% (p=0.085) in Cohort E and 68.9% and 58.2% (p=0.585) in Cohort Others, respectively, suggesting a relationship between low ΔTGF-β and a favorable prognosis only in Cohort E. Conclusions The current study showed the trend in the higher frequency of decreased TGF-β, as well as the important relationship between decreased TGF-β and a favorable prognosis in patients treated with E compared with those receiving other chemotherapies. As the next step, further biomarker analyses including cytokines and chemokines, and immunological analyses are planned. Citation Format: Takahiro Nakayama, Tersuhiro Yoshinami, Fumie Fujisawa, Minako Nishio, Takashi Yamanaka, Toshinari Yamashita, Chiya Oshiro, Ayaka Izui, Nobumoto Tomioka, Hideki Maeda, Masafumi Shimoda, Kenzo Shimazu, Michiko Tsuneizumi, Ryoichi Matsunuma, Hiroko Bando, Aya Ueda, Hiroyuki Yasojima, Kumiko Okada, Kenichi Inoue, Yuichiro Kai, Katsuhide Yoshidome, Hidetoshi Kawaguchi, Masayuki Nagahashi, Kazuteru Oshima, Shinichiro Kashiwagi, Tsutomu Iwasa, Kanae Taruno, Shigeru Tsuyuki, Fumine Tsukamoto, Takashi Morimoto, Nobuyoshi Kittaka, Toru Higuchi, Yoichi Naito, Ryotaro Saita, Hiroyoshi Nishikawa, Daisuke Sugiyama, Yasuo Miyoshi, Yohei Uchida, Tomomi Yamada, Norikazu Masuda. Prospective study on eribulin efficacy in advanced and metastatic breast cancer: changes in TGF-β compared to other standard chemotherapy agents (KBCSG-TR 2018, POTENTIAL) abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-06-04.