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Original Article | Open Access

Phase Ⅱ study of apatinib in combination with oral vinorelbine in heavily pretreated HER2-negative metastatic breast cancer and clinical implications of monitoring ctDNA

Anjie Zhu1,2, Peng Yuan3 ( ), Nanlin Hu1, Mingzhou Li1, Wenmiao Wang4, Xue Wang3, Jian Yue3, Jiayu Wang1, Yang Luo1, Fei Ma1, Pin Zhang1, Qing Li1, Binghe Xu1, Shanbo Cao5, Giuseppe Lippi6, Yoichi Naito7, Mohammed A. Osman8, Gustavo N. Marta9, Gianluca Franceschini10, Armando Orlandi11
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
Department of VIP Medical Services, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
AcornMed Biotechnology Co., Ltd., Beijing 101102, China
Section of Clinical Biochemistry, University Hospital of Verona, Verona 37100, Italy
Department of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa 277-8577, Japan
Clinical Oncology, General Organization for Teaching Hospitals, Cairo 11435, Egypt
Department of Radiation Oncology, Hospital Sírio-Libanês, Sao Paulo 01308-050, Brazil
Multidisciplinary Breast Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00176, Italy
Unit of Medical Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma 00176, Italy
Show Author Information

Abstract

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.

Keywords

Metastatic breast cancerctDNAoral vinorelbineapatinib

Electronic Supplementary Material

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Cancer Biology & Medicine
Volume 18 Issue 3,
August 2021
Pages 875-887
DOI: 10.20892/j.issn.2095-3941.2020.0418
Cite this article:
Zhu A, Yuan P, Hu N, et al. Phase Ⅱ study of apatinib in combination with oral vinorelbine in heavily pretreated HER2-negative metastatic breast cancer and clinical implications of monitoring ctDNA. Cancer Biology & Medicine, 2021, 18(3): 875-887. https://doi.org/10.20892/j.issn.2095-3941.2020.0418

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Received: 21 July 2020
Accepted: 11 November 2020
Published: 01 August 2021
©2021 Cancer Biology & Medicine.

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