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: Xichun Hu, Jian Zhang, Binghe Xu, Zefei Jiang, Joseph Ragaz, Zhongsheng Tong, Qingyuan Zhang, Xiaojia Wang, Jifeng Feng, Danmei Pang, Minhao Fan, Jin Li, Biyun Wang, Zhonghua Wang, Qunling Zhang, Si Sun, Chunmei Liao
• Journal: International journal of cancer (Int J Cancer) Vol. 135 Issue 8 Pg. 1961-9 (Oct 15 2014) ISSN: 1097-0215 [Electronic] United States
• PMID: 24604288 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 UICC.

Chemical References

• Antineoplastic Agents
• Pyridines
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• apatinib
• KDR protein, human
• Vascular Endothelial Growth Factor Receptor-2

Topics

• Adult
• Aged
• Antineoplastic Agents (pharmacology, therapeutic use)
• Disease-Free Survival
• Drug Resistance, Neoplasm
• Female
• Humans
• Kaplan-Meier Estimate
• Lung Neoplasms (blood, drug therapy, mortality, secondary)
• Lymphatic Metastasis
• Middle Aged
• Pyridines (pharmacology, therapeutic use)
• Triple Negative Breast Neoplasms (blood, drug therapy, mortality, pathology)
• Vascular Endothelial Growth Factor A (blood)
• Vascular Endothelial Growth Factor Receptor-2 (antagonists & inhibitors, blood)