Skip to main content
Top
Published in: BMC Cancer 1/2021

Open Access 01-12-2021 | Gallbladder Cancer | Research article

The efficacy and safety of apatinib treatment for patients with advanced or recurrent biliary tract cancer: a retrospective study

Authors: Caiyun Nie, Huifang Lv, Yishu Xing, Beibei Chen, Weifeng Xu, Jianzheng Wang, Xiaobing Chen

Published in: BMC Cancer | Issue 1/2021

Login to get access

Abstract

Introduction

The present study aims to evaluate the efficacy and safety of apatinib monotherapy or combination therapy for patients with advanced or recurrent biliary tract cancer (BTC).

Methods

Twenty-eight patients with advanced or recurrent BTC who progressed after prior systemic therapies and treated with apatinib from January 2017 to June 2019 were enrolled in this retrospective and observational study. The primary end point was progression free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and toxicity.

Results

A total of 28 patients with advanced or recurrent BTC who progressed after prior systemic therapies received apatinib monotherapy or combination therapy (with capecitabine, S-1, oxaliplatin, irinotecan or PD-1 inhibitor), including 9 cases of gallbladder cancer and 19 cases of cholangiocarcinoma. Six patients achieved PR, 15 patients had SD and 7 patients had PD. Median progression-free survival (PFS) and overall survival (OS) was 4.3 months (95%CI = 1.8–6.8) and 6.2 months (95% CI = 4.6–7.8) respectively. The ORR and DCR were 21.4% (6/28) and 75.0% (21/28), respectively. Most of the adverse events were grade 1–2 in severity, apatinib treatment was well tolerated.

Conclusions

Apatinib monotherapy or combination therapy can improve PFS in patients with advanced or recurrent BTC who progressed after prior systemic therapies, and adverse reactions can be well tolerated. Our study support apatinib therapy as a feasible therapeutic strategy in advanced or recurrent BTC.
Appendix
Available only for authorised users
Literature
1.
go back to reference Bridgewater JA, Goodman KA, Kalyan A, Mulcahy MF. Biliary tract Cancer: epidemiology, radiotherapy, and molecular profiling. Am Soc Clin Oncol Educ Book. 2016;35:e194–203.CrossRef Bridgewater JA, Goodman KA, Kalyan A, Mulcahy MF. Biliary tract Cancer: epidemiology, radiotherapy, and molecular profiling. Am Soc Clin Oncol Educ Book. 2016;35:e194–203.CrossRef
2.
go back to reference Shaib Y, El-Serag HB. The epidemiology of cholangiocarcinoma. Semin Liver Dis. 2004;24(2):115–25.CrossRef Shaib Y, El-Serag HB. The epidemiology of cholangiocarcinoma. Semin Liver Dis. 2004;24(2):115–25.CrossRef
3.
go back to reference Marks EI, Yee NS. Molecular genetics and targeted therapeutics in biliary tract carcinoma. World J Gastroenterol. 2016;22(4):1335–47.CrossRef Marks EI, Yee NS. Molecular genetics and targeted therapeutics in biliary tract carcinoma. World J Gastroenterol. 2016;22(4):1335–47.CrossRef
4.
go back to reference Sirica AE, Gores GJ, Groopman JD, Selaru FM, Strazzabosco M, Wei Wang X, Zhu AX. Intrahepatic Cholangiocarcinoma: continuing challenges and translational advances. Hepatology. 2019;69(4):1803–15.CrossRef Sirica AE, Gores GJ, Groopman JD, Selaru FM, Strazzabosco M, Wei Wang X, Zhu AX. Intrahepatic Cholangiocarcinoma: continuing challenges and translational advances. Hepatology. 2019;69(4):1803–15.CrossRef
5.
go back to reference Li J, Qin S, Xu J, Xiong J, Wu C, Bai Y, Liu W, Tong J, Liu Y, Xu R, et al. Randomized, double-blind, placebo-controlled phase III trial of Apatinib in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of the stomach or Gastroesophageal junction. J Clin Oncol. 2016;34(13):1448–54.CrossRef Li J, Qin S, Xu J, Xiong J, Wu C, Bai Y, Liu W, Tong J, Liu Y, Xu R, et al. Randomized, double-blind, placebo-controlled phase III trial of Apatinib in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of the stomach or Gastroesophageal junction. J Clin Oncol. 2016;34(13):1448–54.CrossRef
6.
go back to reference Song ZZ, Zhao LF, Zuo J, Fan ZS, Wang L, Wang YD. Clinical outcomes and safety of Apatinib Mesylate in the treatment of advanced non-squamous non-small cell lung Cancer in patients who progressed after standard therapy and analysis of the KDR gene polymorphism. Onco Targets Ther. 2020;13:603–13.CrossRef Song ZZ, Zhao LF, Zuo J, Fan ZS, Wang L, Wang YD. Clinical outcomes and safety of Apatinib Mesylate in the treatment of advanced non-squamous non-small cell lung Cancer in patients who progressed after standard therapy and analysis of the KDR gene polymorphism. Onco Targets Ther. 2020;13:603–13.CrossRef
7.
go back to reference Zhen L, Jiali C, Yong F, Han X, Hongming P, Weidong H. The efficacy and safety of Apatinib treatment for patients with Unresectable or relapsed liver Cancer: a retrospective study. J Cancer. 2018;9(16):2773–7.CrossRef Zhen L, Jiali C, Yong F, Han X, Hongming P, Weidong H. The efficacy and safety of Apatinib treatment for patients with Unresectable or relapsed liver Cancer: a retrospective study. J Cancer. 2018;9(16):2773–7.CrossRef
8.
go back to reference Zhang J, Li A, Jiang Q, Zheng F, Zhu H. Efficacy and safety of Apatinib treatment in platinum-resistant recurrent epithelial ovarian Cancer: a real world study. Drug Des Devel Ther. 2019;13:3913–8.CrossRef Zhang J, Li A, Jiang Q, Zheng F, Zhu H. Efficacy and safety of Apatinib treatment in platinum-resistant recurrent epithelial ovarian Cancer: a real world study. Drug Des Devel Ther. 2019;13:3913–8.CrossRef
9.
go back to reference Zhu A, Yuan P, Wang J, Fan Y, Luo Y, Cai R, Zhang P, Li Q, Ma F, Xu B. Apatinib combined with chemotherapy in patients with previously treated advanced breast cancer: An observational study. Oncol Lett. 2019;17(6):4768–78.PubMedPubMedCentral Zhu A, Yuan P, Wang J, Fan Y, Luo Y, Cai R, Zhang P, Li Q, Ma F, Xu B. Apatinib combined with chemotherapy in patients with previously treated advanced breast cancer: An observational study. Oncol Lett. 2019;17(6):4768–78.PubMedPubMedCentral
10.
go back to reference Xin M, Xie Q, Ma L, An G, Xiao J, Li J, Liu X, Gao P, Liang J, Li Y. Synergistic anti-tumour effects of Clostridium butyricum in combination with apatinib in CT26 colorectal tumour-bearing mice. Anti-Cancer Drugs. 2019;30(10):991–7.CrossRef Xin M, Xie Q, Ma L, An G, Xiao J, Li J, Liu X, Gao P, Liang J, Li Y. Synergistic anti-tumour effects of Clostridium butyricum in combination with apatinib in CT26 colorectal tumour-bearing mice. Anti-Cancer Drugs. 2019;30(10):991–7.CrossRef
11.
go back to reference Zhu B, Li J, Xie Q, Diao L, Gai L, Yang W. Efficacy and safety of apatinib monotherapy in advanced bone and soft tissue sarcoma: An observational study. Cancer Biol Ther. 2018;19(3):198–204.CrossRef Zhu B, Li J, Xie Q, Diao L, Gai L, Yang W. Efficacy and safety of apatinib monotherapy in advanced bone and soft tissue sarcoma: An observational study. Cancer Biol Ther. 2018;19(3):198–204.CrossRef
12.
go back to reference Huang M, Huang B, Li G, Zeng S. Apatinib affect VEGF-mediated cell proliferation, migration, invasion via blocking VEGFR2/RAF/MEK/ERK and PI3K/AKT pathways in cholangiocarcinoma cell. BMC Gastroenterol. 2018;18(1):169.CrossRef Huang M, Huang B, Li G, Zeng S. Apatinib affect VEGF-mediated cell proliferation, migration, invasion via blocking VEGFR2/RAF/MEK/ERK and PI3K/AKT pathways in cholangiocarcinoma cell. BMC Gastroenterol. 2018;18(1):169.CrossRef
13.
go back to reference Ghidini M, Pizzo C, Botticelli A, Hahne JC, Passalacqua R, Tomasello G, Petrelli F. Biliary tract cancer: current challenges and future prospects. Cancer Manag Res. 2019;11:379–88.CrossRef Ghidini M, Pizzo C, Botticelli A, Hahne JC, Passalacqua R, Tomasello G, Petrelli F. Biliary tract cancer: current challenges and future prospects. Cancer Manag Res. 2019;11:379–88.CrossRef
14.
go back to reference Valle JW, Lamarca A, Goyal L, Barriuso J, Zhu AX. New horizons for precision medicine in biliary tract cancers. Cancer Discov. 2017;7(9):943–62.CrossRef Valle JW, Lamarca A, Goyal L, Barriuso J, Zhu AX. New horizons for precision medicine in biliary tract cancers. Cancer Discov. 2017;7(9):943–62.CrossRef
15.
go back to reference Ghosn M, Kourie HR, El Rassy E, Chebib R, El Karak F, Hanna C, Nasr D. Optimum chemotherapy for the management of advanced biliary tract cancer. World J Gastroenterol. 2015;21(14):4121–5.CrossRef Ghosn M, Kourie HR, El Rassy E, Chebib R, El Karak F, Hanna C, Nasr D. Optimum chemotherapy for the management of advanced biliary tract cancer. World J Gastroenterol. 2015;21(14):4121–5.CrossRef
16.
go back to reference Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362(14):1273–81.CrossRef Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362(14):1273–81.CrossRef
17.
go back to reference Mizusawa J, Morizane C, Okusaka T, Katayama H, Ishii H, Fukuda H, Furuse J. Hepatobiliary, pancreatic oncology Group of the Japan Clinical Oncology G: randomized phase III study of gemcitabine plus S-1 versus gemcitabine plus cisplatin in advanced biliary tract cancer: Japan clinical oncology group study (JCOG1113, FUGA-BT). Jpn J Clin Oncol. 2016;46(4):385–8.CrossRef Mizusawa J, Morizane C, Okusaka T, Katayama H, Ishii H, Fukuda H, Furuse J. Hepatobiliary, pancreatic oncology Group of the Japan Clinical Oncology G: randomized phase III study of gemcitabine plus S-1 versus gemcitabine plus cisplatin in advanced biliary tract cancer: Japan clinical oncology group study (JCOG1113, FUGA-BT). Jpn J Clin Oncol. 2016;46(4):385–8.CrossRef
18.
go back to reference Morizane C, Okusaka T, Mizusawa J, Katayama H, Ueno M, Ikeda M, Ozaka M, Okano N, Sugimori K, Fukutomi A, et al. Combination gemcitabine plus S-1 versus gemcitabine plus cisplatin for advanced/recurrent biliary tract cancer: the FUGA-BT (JCOG1113) randomized phase III clinical trial. Ann Oncol. 2019;30(12):1950–8.CrossRef Morizane C, Okusaka T, Mizusawa J, Katayama H, Ueno M, Ikeda M, Ozaka M, Okano N, Sugimori K, Fukutomi A, et al. Combination gemcitabine plus S-1 versus gemcitabine plus cisplatin for advanced/recurrent biliary tract cancer: the FUGA-BT (JCOG1113) randomized phase III clinical trial. Ann Oncol. 2019;30(12):1950–8.CrossRef
19.
go back to reference Tsimberidou AM. Targeted therapy in cancer. Cancer Chemother Pharmacol. 2015;76(6):1113–32.CrossRef Tsimberidou AM. Targeted therapy in cancer. Cancer Chemother Pharmacol. 2015;76(6):1113–32.CrossRef
20.
go back to reference Kaavya J, Mahalaxmi I, Devi SM, Santhy KS, Balachandar V. Targeting phosphoinositide-3-kinase pathway in biliary tract cancers: a remedial route? J Cell Physiol. 2019;234(6):8259–73.CrossRef Kaavya J, Mahalaxmi I, Devi SM, Santhy KS, Balachandar V. Targeting phosphoinositide-3-kinase pathway in biliary tract cancers: a remedial route? J Cell Physiol. 2019;234(6):8259–73.CrossRef
21.
go back to reference Mahipal A, Tella SH, Kommalapati A, Anaya D, Kim R. FGFR2 genomic aberrations: Achilles heel in the management of advanced cholangiocarcinoma. Cancer Treat Rev. 2019;78:1–7.CrossRef Mahipal A, Tella SH, Kommalapati A, Anaya D, Kim R. FGFR2 genomic aberrations: Achilles heel in the management of advanced cholangiocarcinoma. Cancer Treat Rev. 2019;78:1–7.CrossRef
22.
go back to reference Mehrotra R, Tulsyan S, Hussain S, Mittal B, Singh Saluja S, Singh S, Tanwar P, Khan A, Javle M, Hassan MM, et al. Genetic landscape of gallbladder cancer: global overview. Mutat Res. 2018;778:61–71.CrossRef Mehrotra R, Tulsyan S, Hussain S, Mittal B, Singh Saluja S, Singh S, Tanwar P, Khan A, Javle M, Hassan MM, et al. Genetic landscape of gallbladder cancer: global overview. Mutat Res. 2018;778:61–71.CrossRef
23.
go back to reference Mishra SK, Kumari N, Krishnani N. Molecular pathogenesis of gallbladder cancer: An update. Mutat Res. 2019;816-818:111674.CrossRef Mishra SK, Kumari N, Krishnani N. Molecular pathogenesis of gallbladder cancer: An update. Mutat Res. 2019;816-818:111674.CrossRef
24.
go back to reference Peng H, Zhang Q, Li J, Zhang N, Hua Y, Xu L, Deng Y, Lai J, Peng Z, Peng B, et al. Apatinib inhibits VEGF signaling and promotes apoptosis in intrahepatic cholangiocarcinoma. Oncotarget. 2016;7(13):17220–9.CrossRef Peng H, Zhang Q, Li J, Zhang N, Hua Y, Xu L, Deng Y, Lai J, Peng Z, Peng B, et al. Apatinib inhibits VEGF signaling and promotes apoptosis in intrahepatic cholangiocarcinoma. Oncotarget. 2016;7(13):17220–9.CrossRef
25.
go back to reference Wang LY, Gong S, Gao LP, Hou LX, He W. Apatinib for treating advanced intrahepatic cholangiocarcinoma after failed chemotherapy: a case report and literature review. Medicine (Baltimore). 2018;97(49):e13372.CrossRef Wang LY, Gong S, Gao LP, Hou LX, He W. Apatinib for treating advanced intrahepatic cholangiocarcinoma after failed chemotherapy: a case report and literature review. Medicine (Baltimore). 2018;97(49):e13372.CrossRef
26.
go back to reference Zheng Y, Tu X, Zhao P, Jiang W, Liu L, Tong Z, Zhang H, Yan C, Fang W, Wang W. A randomised phase II study of second-line XELIRI regimen versus irinotecan monotherapy in advanced biliary tract cancer patients progressed on gemcitabine and cisplatin. Br J Cancer. 2018;119(3):291–5.CrossRef Zheng Y, Tu X, Zhao P, Jiang W, Liu L, Tong Z, Zhang H, Yan C, Fang W, Wang W. A randomised phase II study of second-line XELIRI regimen versus irinotecan monotherapy in advanced biliary tract cancer patients progressed on gemcitabine and cisplatin. Br J Cancer. 2018;119(3):291–5.CrossRef
27.
go back to reference Blair AB, Murphy A. Immunotherapy as a treatment for biliary tract cancers: a review of approaches with an eye to the future. Curr Probl Cancer. 2018;42(1):49–58.CrossRef Blair AB, Murphy A. Immunotherapy as a treatment for biliary tract cancers: a review of approaches with an eye to the future. Curr Probl Cancer. 2018;42(1):49–58.CrossRef
Metadata
Title
The efficacy and safety of apatinib treatment for patients with advanced or recurrent biliary tract cancer: a retrospective study
Authors
Caiyun Nie
Huifang Lv
Yishu Xing
Beibei Chen
Weifeng Xu
Jianzheng Wang
Xiaobing Chen
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-021-07907-4

Other articles of this Issue 1/2021

BMC Cancer 1/2021 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

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