Hiroshi Ishiguro, Yasuo Miyoshi, Hiroyuki Yasojima, Junichiro Watanabe, Toshimi Takano, Akihiko Shimomura, Eriko Tokunaga, Toru Mukohara, Yasuto Naoi, Daiko Matsuoka, Shiori Okumura, Yohei Otake, Takuya Suzuki, Takao Takase, Taro Semba, Ziming Zhao, Kan Yonemori
These results highlight the antitumor activity and manageable safety profile of E7389-LF, indicating the potential of E7389-LF as a 1L treatment for patients with HER2-negative breast cancer, warranting further study.
BACKGROUND: There is an ongoing need for first-line (1L) chemotherapies for metastatic HER2-negative breast cancer. This study evaluated the efficacy and safety profile of the dose-expansion part 6 of Study 114 in patients receiving E7389-LF as a 1L chemotherapy for metastatic/advanced HER2-negative breast cancer.
METHODS: Japanese patients (≥ 20 years of age) with confirmed HER2-negative breast cancer (HER2-0 or HER2-low) were enrolled; subgroup analyses included luminal-like and triple-negative breast cancer tumors. Eligible patients had ≥ 1 measurable lesion per Response Evaluation Criteria in Solid Tumor version 1.1 (RECIST v1.1) and had not received prior chemotherapy for advanced/metastatic disease. Objectives included safety, efficacy, and biomarker changes. Tumors were assessed by investigators per RECIST v1.1.
RESULTS: Twenty-six patients received E7389-LF. Overall, 24 patients (92.3%) had discontinued treatment by the data cutoff date (October 18, 2023). Most common treatment-related adverse events (TRAEs) of any grade were alopecia (88.5%), neutropenia (88.5%; grade ≥ 3, 76.9%), and thrombocytopenia (84.6%; grade ≥ 3, 34.6%). Three patients discontinued due to TRAEs. No patient showed a complete response, and 8 (30.8%) had confirmed partial responses, for an objective response rate of 30.8%. Median progression-free survival (PFS) was 8.1 months overall (patients with luminal breast cancer [n = 22]: 8.1 months; triple-negative breast cancer [n = 4]: 9.8 months). Median overall survival was not reached at 22.7 months of follow-up. Median PFS on next-line therapy was 20.6 months. Changes in vasculature- and IFNγ-related biomarkers were observed in all patients who received E7389-LF.
CONCLUSIONS: These results highlight the antitumor activity and manageable safety profile of E7389-LF, indicating the potential of E7389-LF as a 1L treatment for patients with HER2-negative breast cancer, warranting further study.
CLINICAL TRIALS REGISTRATION: NCT03207672. Registered 5 July 2017.