Abstract P2-10-01: Phase II study of antiangiogenic tyrosine kinase inhibitor apatinib in combination with oral vinorelbine in heavily pretreated HER2-negative advanced breast cancer

Background: Metastatic breast cancer remains an incurable disease, and clinical benefit and progression-free survival are the main end points in advanced setting. Targeted therapies have shown promising potentials in HER2-positive breast cancer, but with uncertain effects in HER2-negative breast cancer, especially when the disease is progressing rapidly. The regimen of antiangiogenic therapy in combination with chemotherapy had been studied for years and gained improved efficacy. Apatinib is an oral, highly potent tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2. PhaseIIclinical trials of Apatinib single agent had presented objective response and manageable toxicity in heavily pretreated, metastatic breast cancer. Oral vinorelbine represents a good choice for its toxicity and activity in anthracycline and taxane-pretreated breast cancer patients. This all-oral study aims to investigate the efficacy and safety of the oral vinorelbine-apatinib combination in pre-treated metastatic breast cancer. Methods: This study enrolled patients with HER2-negative advanced breast cancer, pretreated with anthracycline/taxanes, and who failed in the metastatic setting at least one prior chemotherapy or endocrine therapy when hormone receptor is positive. Patients were treated with apatinib 500mg/425mg daily plus oral vinorelbine 60mg/m2 day1,8,15 every 3 weeks/cycle. Patients eligible were evaluated by CT or MRI scan at baseline and every 2 cycles (6 weeks) there after until disease progressed. The primary endpoint wasPFS. The secondary endpoints were objective response rate, clinical benefit rate, OS, and safety. Results: 40 patients were enrolled with a median age of 55 (30-70) years. First 17 patients started apatinib at the dose of 500mg/day. Considering safety issues, a lower dose of apatinib 425mg/day was subsequently started as the initial dose after these 17 patients recruited. 26(65.0%) patients experienced treatment delay and 20(50.0%) patients experienced dose modification during treatment. Median follow-up time was 10.3 months. Of all 40 patients, median PFS was 5.4 months (95% CI, 3.4m–7.3m). Median OS was not reached. 32 patients were eligible for efficacy analysis. ORR was 15.6% (5/32). CBR was 46.9% (15/32). Patients with triple-negative breast cancer or who received combined therapy as second line treatment gained better ORR and longer median PFS. The most common adverse events of all grades included gastrointestinal reaction (70.0%), myelosuppression (67.5%), hypertension(62.5%), pain(60.0%), malaise(52.5%), anorexia(50.0%), elevated transaminase(47.5%), hand-foot reaction (47.5%), proteinuria (37.5%), and elevated bilirubin(32.5%). Proteinuria, treatment delay, and ECOG performance status were independent predictive factors for PFS.Conclusions: The all-oral therapy of antiangiogenic tyrosine kinase inhibitor apatinib plus vinorelbine presented objective efficacy in advanced HER2-negative breast cancer who failed from first-line therapy, with acceptable and manageable toxicity. Citation Format: Zhu A, Yuan P, Wang J, Fan Y, Luo Y, Cai R, Zhang P, Li Q, Ma F, Xu B. Phase II study of antiangiogenic tyrosine kinase inhibitor apatinib in combination with oral vinorelbine in heavily pretreated HER2-negative advanced breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-10-01.