A prospective, single-arm, single-center, exploratory clinical study of anlotinib combined with irinotecan in second-line and above treatment of HER-2–negative advanced breast cancer.

person Ying Zhang Affiliated Hospital of Jiangnan University, Wuxi, China info_outline Ying Zhang, Wenhuan Xu, Yutian Zhao, Xuedan Guo, Tingting Hong, Yidan Yan, Xiaohong Wu

Authors person Ying Zhang Affiliated Hospital of Jiangnan University, Wuxi, China info_outline Ying Zhang, Wenhuan Xu, Yutian Zhao, Xuedan Guo, Tingting Hong, Yidan Yan, Xiaohong Wu Organizations Affiliated Hospital of Jiangnan University, Wuxi, China, Department of Medical Oncology, Affiliated Hospital of Jiangnan University, Wuxi, China, Department of Medical Oncology, Wuxi No.2 People’s Hospital, Wuxi, China, Jiangnan University Affiliated Hospital, Wuxi, China Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Chia Tai Tianqing Pharmaceutical Group Co., Ltd. Background: The group of HER2-negative accounts for 70-80% of breast cancer and effective treatments for heavily pretreated patients with HER2-negative metastatic breast cancer are urgently needed. Irinotecan is a semi-synthetic water-soluble camptothecin derivative which can be used as a chemotherapeutic agent for HER2-negative breast cancer after failure of anthracycline and taxanes treatments. Anlotinib is a novel multitarget tyrosine kinase inhibitor targeting VEGFR, PDGFR, FGFR, and c-Kit. This study aimed to evaluate the efficacy and safety of irinotecan combined with anlotinib in second-line and above treatment of HER-2 negative advanced breast cancer. (ChiCTR2000037448) Methods: This open-label, single-arm, phase II study enrolled women aged 18 years and older with HER2-negative breast cancer who underwent ≥1 line chemotherapy, All patients were treated with irinotecan (60mg/m2, administered intravenously on Days 1 and 8 of each 21 day cycle) and anlotinib (12mg, qd, administered orally on Days 1-14 of each 21 day cycle). The primary endpoint was objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), disease control rate (DCR), overall survival (OS) and safety. Results: From November 2020 to November 2022, 14 patients were enrolled in this study. Median follow-up was 10.8 months (95% CI 4.3-17.3). Median PFS was 5.9 months (95% CI 2.0-9.8). Of all the patients whose efficacy could be evaluated (13/14), no patient achieved complete response (CR); 3(23.07%) and 8(61.54%) patients got partial response (PR) and stable disease (SD), respectively. ORR was 23.1% (95% CI 5.0-53.8) and DCR was 84.6% (95% CI 54.6-98.1). OS has not reached. The major treatment-related adverse events (incidence≥10%) were fatigue (42.86%), hypertension (42.86%), neutropenia (28.57%), hand foot syndrome (21.43%) and myelosuppression (14.29%). There is no grade 3/4 adverse events occurred.28.57% (4/14) of patients had dose reductions. Conclusions: The combination of irinotecan and anlotinib showed better treatment response and tolerable toxicity in the treatment of second-line and above patients with HER2-negative metastatic breast cancer. Further studies enrolling more patients are still needed. Clinical trial information: ChiCTR2000037448.

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