Efficacy and safety of eribulin plus gemcitabine in second-line or beyond for patients with HER2-negative metastatic breast cancer (MBC): A multicenter, open-label, single-arm, phase II study.

person Peijian Peng Department of Breast Diseases, The Cancer Center of the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China info_outline Peijian Peng, Xiaolu Xu, Jincai Zhong, Jin-Hui Ye, Zhi-Hui Wang, Hong Wang, Hong Lin, Caiwen Du, Guorong Zou, Jie Ouyang, Ying-ying Shi, Fei Xu, Gengsheng Yu, Yongkui Lu, Yong-Xia Wang, Shi-En Cui, Lu-Zhen Li

Authors person Peijian Peng Department of Breast Diseases, The Cancer Center of the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China info_outline Peijian Peng, Xiaolu Xu, Jincai Zhong, Jin-Hui Ye, Zhi-Hui Wang, Hong Wang, Hong Lin, Caiwen Du, Guorong Zou, Jie Ouyang, Ying-ying Shi, Fei Xu, Gengsheng Yu, Yongkui Lu, Yong-Xia Wang, Shi-En Cui, Lu-Zhen Li Organizations Department of Breast Diseases, The Cancer Center of the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China, The First Affiliated Hospital of Guangxi Medical University, Nanning, China, Department of Breast Oncology, The First People's Hospital of Zhaoqing, Zhaoqing, China, Jiangmen Central Hospital, Jiangmen, China, Department of Breast Surgery, Zhuhai Maternity and Child Health Hospital, Zhuhai, Guangdong Province, People’s Republic of China, Zhuhai, Guangdong, China, Department of Breast Disease, Zhuhai Hospital of lntegrated Traditional Chinese and Western Medicine, Zhuhai, Guangdong, China, Cancer Hospital Chinese Academy Of Medical Sciences, Shenzhen Center, Shenzhen, China, Panyu Central Hospital, Guangzhou, China, Dongguan People's Hospital, No. 3, Dongguan, China, Department of Medical Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China, Guangxi Medical University Cancer Center, Guangxi, China, Dongguan People's Hospital, Dongguan, China, Breast Center, Department of General Surgery, Zhongshan City People's Hospital, Zhongshan, China, Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, China Abstract Disclosures Research Funding No funding sources reported Background: The combination of eribulin and gemcitabine has demonstrated a similar progression-free survival (PFS) benefit as paclitaxel plus gemcitabine, with less neurotoxicity, for patients with MBC who have not received prior cytotoxic chemotherapy. However, the effect of eribulin plus gemcitabine on PFS in second line or beyond remains unclear. Methods: This open-label, single-arm, phase II study (NCT05263882) was conducted at 14 institutions in China. Eligible patients had histologically confirmed HER2-negative MBC and had received at least one prior taxane-containing chemotherapy regimen for advanced disease, and anthracycline-containing regimens in the adjuvant setting. Patients received intravenous infusions of eribulin (1.4 mg/m 2 ) and gemcitabine (1.0 g/m 2 ) on days 1 and 8 of a 21-day cycle. Efficacy outcomes, including PFS, objective response rate (ORR), and disease control rate (DCR), were assessed using RECIST v1.1. Adverse events (AEs) were graded according to NCI-CTC version 5.0. Results: A total of 70 patients were enrolled from November 2021 to October 2023; 47 (71.4%) had HR+HER2- and 18 (28.6%) had triple-negative MBC. The median patient age was 50 years (range: 31-68), and the sites of metastasis were the bone (68.6%), liver (52.9%), lymph nodes (48.6%), lung (44.3%) and brain (10.0%). Patients had received a median of 3 prior lines of systemic treatment, 2 lines of chemotherapy, and 1 line of endocrine treatment. Among all patients, the ORR was 48.6%, the DCR was 92.9% and the median PFS was 7.2 months. For the HR-positive subgroup, the median PFS was 8.4 months, while for the triple-negative subgroup, it was 6.3 months. Among HR+ patients who had received prior CDK4/6 inhibitor treatment, the median PFS was 7.2 months. In the subgroup of HR+ patients who had not received CDK4/6 inhibitor treatment, the median PFS had not been reached. For the HR+ HER2-low subgroup, the median PFS was 8.4 months. The most common grade 3-4 AEs were hematological, including neutropenia (38.6%), leukopenia (31.4%), anemia (24.3%), and thrombocytopenia (15.7%). Grade ≥3 perceived AEs were relatively low. Conclusions: Eribulin plus gemcitabine was effective in heavily pretreated patients with HER2- MBC, while maintaining a predictable and manageable safety profile. Clinical trial information: NCT05263882. Summary of efficacy outcomes. Efficacy Outcomes Total (N=70) HR+HER2- (n=50) TNBC (n=20) Post-CDK4/6i (HR+HER2-) (n=29) CDK4/6i naïve (HR+HER2-) (n=21) HR+HER2-low (n=36) ORR, n (%) 34 (48.6) 25 (50.0) 9 (45.0) 13 (44.8) 12 (57.1) 18 (50.0) DCR, n (%) 65 (92.9) 48 (96.0) 17 (85.0) 28 (96.6) 20 (95.2) 35 (97.2) Median PFS, months (95% CI) 7.2 (5.5, 10.9) 8.4 (5.5, -) 6.3 (3.6, 8.6) 7.2 (5.0, 15.8) -(5.3,-) 8.4 (5.4, 15.8) TNBC, triple-negative breast cancer.

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