E7389-LF as a first-line chemotherapy for patients with metastatic/advanced HER2-negative breast cancer: results from the phase 1 dose-expansion part of study 114

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.