title: Multicenter phase II study of apatinib, a novel VEGFR inhibitor in heavily pretreated patients with metastatic triple-negative breast cancer.
abstract: Apatinib is an oral, highly potent tyrosine-kinase inhibitor targeting VEGFR2. Phase I study showed the recommended dose of 750 mg/day with substantial antitumor activity. This phase II study aims to evaluate the optimum dose level for the efficacy and safety of apatinib monotherapy in heavily pretreated patients with metastatic triple negative breast cancer (mTNBC) in China. Phase IIa was first performed among 25 patients previously treated with anthracycline and/or taxane. All patients received apatinib 750 mg/day p.o. in a 4-week cycle. Subsequently, a phase IIb study of 59 patients was activated, with the endpoint progression-free survival (PFS). The dosage of drug for the Phase IIb was determined according to safety, tolerability and efficacy from the phase IIa study. As a result of toxicity associated with the 750 mg dose in phase IIa, the recommended initial dose of apatinib in the phase IIb was 500 mg/day. In phase IIb, grade 3/4 hematologic toxicities were thrombocytopenia (13.6%), leukopenia (6.8%), neutropenia (3.4%) and anemia (1.7%). The most frequent grade 3/4 nonhematologic toxicities were hand-foot syndrome, proteinuria, hypertension, and increased ALT. In the 56 evaluable patients, overall response rate and clinical benefit rate (CBR) were 10.7 and 25.0%, respectively. Median PFS and overall survival were 3.3 (95% CI 1.7-5.0) and 10.6 (95% CI 5.6-15.7) months, respectively. Our results indicate that apatinib dose of 500 mg rather than 750 mg is the recommended starting dose for the heavily pretreated mTNBC patients with measurable rate of partial response and PFS.
authors.affiliation: Department of Medical Oncology, Fudan University, Shanghai Cancer Center, China, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Xichun
authors.initials: X
authors.lastname: Hu
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Binghe
authors.initials: B
authors.lastname: Xu
authors.forename: Zefei
authors.initials: Z
authors.lastname: Jiang
authors.forename: Joseph
authors.initials: J
authors.lastname: Ragaz
authors.forename: Zhongsheng
authors.initials: Z
authors.lastname: Tong
authors.forename: Qingyuan
authors.initials: Q
authors.lastname: Zhang
authors.forename: Xiaojia
authors.initials: X
authors.lastname: Wang
authors.forename: Jifeng
authors.initials: J
authors.lastname: Feng
authors.forename: Danmei
authors.initials: D
authors.lastname: Pang
authors.forename: Minhao
authors.initials: M
authors.lastname: Fan
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Biyun
authors.initials: B
authors.lastname: Wang
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Wang
authors.forename: Qunling
authors.initials: Q
authors.lastname: Zhang
authors.forename: Si
authors.initials: S
authors.lastname: Sun
authors.forename: Chunmei
authors.initials: C
authors.lastname: Liao
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D064726:Triple Negative Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors / Q000097:blood*
chemical_list: D000970:Antineoplastic Agents; D011725:Pyridines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C553458:apatinib; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: VEGFR2; apatinib; metastatic breast cancer; triple negative