RT Journal Article
SR Electronic
T1 Phase II study of apatinib in combination with oral vinorelbine in heavily pretreated HER2-negative metastatic breast cancer and clinical implications of monitoring ctDNA
JF Cancer Biology and Medicine
JO Cancer Biol Med
FD China Anti-Cancer Association
SP 875
OP 887
DO 10.20892/j.issn.2095-3941.2020.0418
VO 18
IS 3
A1 Anjie Zhu
A1 Peng Yuan
A1 Nanlin Hu
A1 Mingzhou Li
A1 Wenmiao Wang
A1 Xue Wang
A1 Jian Yue
A1 Jiayu Wang
A1 Yang Luo
A1 Fei Ma
A1 Pin Zhang
A1 Qing Li
A1 Binghe Xu
A1 Shanbo Cao
A1 Giuseppe Lippi
A1 Yoichi Naito
A1 Mohammed A. Osman
A1 Gustavo N. Marta
A1 Gianluca Franceschini
A1 Armando Orlandi
YR 2021
UL http://www.cancerbiomed.org/content/18/3/875.abstract
AB Objective: Apatinib is an oral TKI targeting VEGFR-2. Single-agent apatinib treatment has been shown to produce an objective response in patients with pretreated mBC. Oral vinorelbine also holds promise as a treatment of choice in patients with mBC. This study aimed to investigate the efficacy and safety of the oral vinorelbine-apatinib combination in patients with pretreated mBC. In addition, we detected gene variants in ctDNA to explore the therapeutic implications.Methods: This study enrolled patients with HER2-negative mBC who were pretreated with anthracycline/taxanes. Patients were treated with apatinib at 500 mg/425 mg daily plus oral vinorelbine 60 mg/m2 on days 1, 8, and 15 of every cycle (3 weeks). The primary endpoint was PFS. The secondary endpoints were ORR, CBR, OS, and safety. Patients eligible for ctDNA detection were evaluated before and during treatment.Results: Forty patients were enrolled. The median PFS was 5.2 months (95% CI, 3.4–7.0 months), and the median OS was 17.4 months (95% CI, 8.0–27.0 months). The ORR was 17.1% (6/35), and the CBR was 45.7% (16/35). The most common AEs included gastrointestinal reaction, myelosuppression, and hypertension. In 20 patients, ctDNA was detected at baseline and during treatment. A significant difference was found in PFS for undetected vs. detected baseline ctDNA (13.9 months vs. 3.6 months, P = 0.018).Conclusions: All-oral therapy with apatinib plus vinorelbine displayed objective efficacy in patients with heavily pretreated HER2-negative mBC, with acceptable and manageable toxicity profiles. Patients with no gene variant detected and lower variant allele frequencies in ctDNA at baseline showed longer PFS.