Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

Multicenter phase II study of Apatinib in non-triple-negative metastatic breast cancer

Authors: Xichun Hu, Jun Cao, Wenwei Hu, Changping Wu, Yueyin Pan, Li Cai, Zhongsheng Tong, Shusen Wang, Jin Li, Zhonghua Wang, Biyun Wang, Xiaoyu Chen, Hao Yu

Published in: BMC Cancer | Issue 1/2014

Login to get access

Abstract

Background

Apatinib is a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2(VEGFR-2). This study was conducted to assess the efficacy and safety of apatinib in patients with non-triple-negative metastatic breast cancer who had received prior chemotherapy for their metastatic disease.

Methods

This multicenter, open-label, single arm study enrolled patients with non-triple-negative breast cancer, pretreated with anthracycline, taxanes and capecitabine, and who failed in the metastatic setting at least 1 and at most 4 prior chemotherapy regimens and at least one endocrine drug for hormone receptor-positive patients as well as at least one anti-Her2 drug for Her2-positive patients. The primary end point of this study was progression free survival (PFS). Secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and toxicity. Apatinib was administered as 500 mg daily on days 1 through 28 of each 4-week cycle.

Results

38 patients were enrolled with a median age of 49 years (range, 35 to 62 years) and received apatinib for a median of 4 cycles (range from 0 to 10 cycles). 18 (47.4%) patients experienced dose reduction during treatment. The median relative dose intensity (relative to assigned dose for each cycle) was 82% (range, 45.0% to 100.0%). Median follow-up time was 10.1 months. Median PFS of all 38 patients was 4.0 months (95% confidence interval (CI), 2.8 m – 5.2 m). 36 patients were eligible for efficacy analysis. ORR was 16.7% (6/36). DCR was 66.7% (24/36). Median OS was 10.3 months (95% CI, 9.1 m – 11.6 m). The most common grade 3/4 treatment-related AEs were hypertension (20.5%), hand-foot syndrome (10.3%), and proteinuria (5.1%). Of three possibly drug-related SAEs recorded in the study, 2 (3.4%) deaths occurred within 28 days of last treatment and were both considered to be the result of disease progression. The other one was grade 2 diarrhea needing hospitalization.

Conclusions

Apatinib exhibited objective efficacy in heavily pretreated, metastatic non-triple-negative breast cancer with manageable toxicity, and it might be better to be tested in breast cancer with high angiogenesis dependency.

Trial registration

ClinicalTrials.gov: NCT01653561.
Appendix
Available only for authorised users
Literature
1.
Althuis MD, Dozier JD, Anderson WF, Devesa SS, Brinton LA: Global trends in breast cancer incidence and mortality 1973–1997. Int J Epidemiol. 2005, 34 (2): 405-412. 10.1093/ije/dyh414. Epub 2005 Feb 28CrossRefPubMed
2.
Early Breast Cancer Trialists' Collaborative Group (EBCTCG): Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomized trials. Lancet. 2005, 365 (9472): 1687-1717.CrossRef
3.
Banerjee S, Dowsett M, Ashworth A, Martin LA: Mechanisms of disease: angiogenesis and the management of breast cancer. Nat Clin Pract Oncol. 2007, 4: 536-550.CrossRefPubMed
4.
Ferrara N: Vascular endothelial growth factor basic science and clinical progress. Endocr Rev. 2004, 25: 581-611. 10.1210/er.2003-0027.CrossRefPubMed
5.
Miles DW, Chan A, Dirix LY, Cortés J, Pivot X, Tomczak P, Delozier T, Sohn JH, Provencher L, Puglisi F, Harbeck N, Steger GG, Schneeweiss A, Wardley AM, Chlistalla A, Romieu G: Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2010, 28: 3239-3247. 10.1200/JCO.2008.21.6457.CrossRefPubMed
6.
Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, Shenkier T, Cella D, Davidson NE: Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007, 357: 2666-2676. 10.1056/NEJMoa072113.CrossRefPubMed
7.
Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J: RIBBON-1: Randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor r 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011, 29: 1252-1260. 10.1200/JCO.2010.28.0982.CrossRefPubMed
8.
Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS: RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011, 29 (32): 4286-4293. 10.1200/JCO.2010.34.1255. Epub 2011 Oct 11CrossRefPubMed
9.
Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH: Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006, 355 (24): 2542-2550. 10.1056/NEJMoa061884.CrossRefPubMed
10.
Escudier B, Pluzanska A, Koralewski P, Ravaud A, Bracarda S, Szczylik C, Chevreau C, Filipek M, Melichar B, Bajetta E, Gorbunova V, Bay JO, Bodrogi I, Jagiello-Gruszfeld A, Moore N: AVOREN Trial investigators. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet. 2007, 370 (9605): 2103-2111. 10.1016/S0140-6736(07)61904-7.CrossRefPubMed
11.
Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F: Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004, 350 (23): 2335-2342. 10.1056/NEJMoa032691.CrossRefPubMed
12.
Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, Mannel RS, Homesley HD, Fowler J, Greer BE, Boente M, Birrer MJ, Liang SX, Gynecologic Oncology Group: Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011, 365 (26): 2473-2483. 10.1056/NEJMoa1104390.CrossRefPubMed
13.
Mendel DB, Laird AD, Xin X, Louie SG, Christensen JG, Li G, Schreck RE, Abrams TJ, Ngai TJ, Lee LB, Murray LJ, Carver J, Chan E, Moss KG, Haznedar JO, Sukbuntherng J, Blake RA, Sun L, Tang C, Miller T, Shirazian S, McMahon G, Cherrington JM: In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascularendothelial growth factor and platelet-derived growth factor receptors: determination of apharmacokinetic/ pharmacodynamic relationship. Clin Cancer Res. 2003, 9 (1): 327-337.PubMed
14.
Wilhelm S, Carter C, Lynch M, Lowinger T, Dumas J, Smith RA, Schwartz B, Simantov R, Kelley S: Discovery and development of sorafenib: a multikinase inhibitor for treating cancer. Nat Rev Drug Discov. 2006, 5 (10): 835-844. 10.1038/nrd2130.CrossRefPubMed
15.
Bianchi G, Loibl S, Zamagni C, Salvagni S, Raab G, Siena S, Laferriere N, Peña C, Lathia C, Bergamini L, Gianni L: Phase II multicenter, uncontrolled trial of sorafenib in patients with metastatic breast cancer. Anticancer Drugs. 2009, 20: 616-624. 10.1097/CAD.0b013e32832b2ea0.CrossRefPubMed
16.
Moreno-Aspitia A, Morton RF, Hillman DW, Lingle WL, Rowland KM, Wiesenfeld M, Flynn PJ, Fitch TR, Perez EA: Phase II trial of sorafenib in patients with metastatic breast cancer previously exposed to anthracyclines or taxanes: North Central Cancer Treatment Group and Mayo Clinic Trial N0336. J Clin Oncol. 2009, 27 (1): 11-5. Epub 2008 Dec 1CrossRefPubMed
17.
Burstein HJ, Elias AD, Rugo HS, Cobleigh MA, Wolff AC, Eisenberg PD, Lehman M, Adams BJ, Bello CL, DePrimo SE, Baum CM, Miller KD: Phase II study of sunitinib malate, an oral multitargeted tyrosine kinase inhibitor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2008, 26: 1810-1816. 10.1200/JCO.2007.14.5375.CrossRefPubMed
18.
Li J, Zhao X, Chen L, Guo H, Lv F, Jia K, Yv K, Wang F, Li C, Qian J, Zheng C, Zuo Y: Safety and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor YN968D1 in patients with advanced malignancies. BMC Cancer. 2010, 10: 529-10.1186/1471-2407-10-529.CrossRefPubMedPubMedCentral
19.
Li J, Qin S, Xu J, Guo W, Xiong J, Bai Y, Sun G, Yang Y, Wang L, Xu N, Cheng Y, Wang Z, Zheng L, Tao M, Zhu X, Ji D, Liu X, Yu H: Apatinib for chemotherapy-refractory advanced metastatic gastric cancer: results from a randomized, placebo-controlled, parallel-arm, phase II trial. J Clin Oncol. 2013, 31 (26): 3219-3225. 10.1200/JCO.2013.48.8585.CrossRefPubMed
20.
Hu X, Zhang J, Xu B, Jiang Z, Ragaz J, Tong Z, Zhang Q, Wang X, Feng J, Pang D, Fan M, Li J, Wang B, Wang Z, Zhang Q, Sun S, Liao C: Multicenter phase II study of apatinib, a novel VEGFR inhibitor in heavily pretreated patients with metastatic triple-negative breast cancer. Int J Cancer. 2014, Epub ahead of print
21.
Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Freeman S, Schwartz B, Shan M, Simantov R, Bukowski RM, TARGET Study Group: Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007, 356 (2): 125-134. 10.1056/NEJMoa060655.CrossRefPubMed
22.
Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Häussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J, SHARP Investigators Study Group: Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008, 359 (4): 378-390. 10.1056/NEJMoa0708857.CrossRefPubMed
23.
Cobleigh MA, Langmuir VK, Sledge GW, Miller KD, Haney L, Novotny WF, Reimann JD, Vassel A: A phase I/II dose-escalation trial of bevacizumab in previously treated metastatic breast cancer. Semin Oncol. 2003, 30 (5 Suppl 16): 117-124.CrossRefPubMed
24.
Baselga J, Segalla JG, Roché H, Del Giglio A, Pinczowski H, Ciruelos EM, Filho SC, Gómez P, Van Eyll B, Bermejo B, Llombart A, Garicochea B, Durán MÁ, Hoff PM, Espié M, de Moraes AA, Ribeiro RA, Mathias C, Gil Gil M, Ojeda B, Morales J, Kwon Ro S, Li S, Costa F: Sorafenib in combination with capecitabine: an oral regimen for patients with HER2-negative locally advanced or metastatic breast cancer. J Clin Oncol. 2012, 30: 1484-1491. 10.1200/JCO.2011.36.7771.CrossRefPubMed
25.
Schwartzberg LS, Tauer KW, Hermann RC, Makari-Judson G, Isaacs C, Beck JT, Kaklamani V, Stepanski EJ, Rugo HS, Wang W, Bell-McGuinn K, Kirshner JJ, Eisenberg P, Emanuelson R, Keaton M, Levine E, Medgyesy DC, Qamar R, Starr A, Ro SK, Lokker NA, Hudis CA: Sorafenib or placebo with either gemcitabine or capecitabine in patients with HER-2-negativeadvanced breast cancer that progressed during or after bevacizumab. Clin Cancer Res. 2013, 19 (10): 2745-2754. 10.1158/1078-0432.CCR-12-3177.CrossRefPubMed
26.
Gradishar WJ, Kaklamani V, Sahoo TP, Lokanatha D, Raina V, Bondarde S, Jain M, Ro SK, Lokker NA, Schwartzberg L: A double-blind, randomised, placebo-controlled, phase 2b study evaluating sorafenib in combination with paclitaxel as a first-line therapy in patients with HER2-negative advanced breast cancer. Eur J Cancer. 2013, 49: 312-322. 10.1016/j.ejca.2012.08.005.CrossRefPubMed
27.
Mariani G, Burdaeva O, Roman L, Staroslawska E, Udovitsa D, Driol P, Goisis G, Zamagni C, Semiglazov V, Gianni L: A double-blind, randomized phase IIb study evaluating the efficacy and safety of sorafenib compared to placebo when administered in combination with docetaxel and/or letrozole in patients with metastatic breast cancer (MDC): FM-B07-01 Trial [abstract]. Eur J Cancer. 2011, 47 (Suppl 2): 10-CrossRef
28.
Rugo HS, Stopeck AT, Joy AA, Chan S, Verma S, Lluch A, Liau KF, Kim S, Bycott P, Rosbrook B, Bair AH, Soulieres D: Randomized, placebo-controlled, double-blind, phase II study of axitinib plus docetaxel versus docetaxel plus placebo in patients with metastatic breast cancer. J Clin Oncol. 2011, 29 (18): 2459-2465. 10.1200/JCO.2010.31.2975.CrossRefPubMed
29.
Tang JR, Markham NE, Lin YJ, McMurtry IF, Maxey A, Kinsella JP, Abman SH: Inhaled nitric oxide attenuates pulmonary hypertension and improves lung growth in infant rats after neonatal treatment with a VEGF receptor inhibitor. Am J Physiol Lung Cell Mol Physiol. 2004, 287 (2): L344-51. 10.1152/ajplung.00291.2003.CrossRefPubMed
Metadata
Title
Multicenter phase II study of Apatinib in non-triple-negative metastatic breast cancer
Authors
Xichun Hu
Jun Cao
Wenwei Hu
Changping Wu
Yueyin Pan
Li Cai
Zhongsheng Tong
Shusen Wang
Jin Li
Zhonghua Wang
Biyun Wang
Xiaoyu Chen
Hao Yu
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-820

Other articles of this Issue 1/2014

BMC Cancer 1/2014 Go to the issue

Research article

Second primary cancer risk - the impact of applying different definitions of multiple primaries: results from a retrospective population-based cancer registry study

Research article

Inhibition of the JAK2/STAT3 pathway in ovarian cancer results in the loss of cancer stem cell-like characteristics and a reduced tumor burden

Research article

Pattern of use of radiotherapy for lung cancer: a descriptive study

Study protocol

Ion Prostate Irradiation (IPI) – a pilot study to establish the safety and feasibility of primary hypofractionated irradiation of the prostate with protons and carbon ions in a raster scan technique

Research article

Transarterial infusion chemotherapy with cisplatin plus S-1 for hepatocellular carcinoma treatment: a phase I trial

Research article

Boosting Wnt activity during colorectal cancer progression through selective hypermethylation of Wnt signaling antagonists
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits