Efficacy and Safety of Apatinib in Treatment of Unresectable Intrahepatic Cholangiocarcinoma: An Observational Study

Yubin Hu, Hailan Lin, Mingzhi Hao, Yan Zhou, Qizhong Chen, Zhangxian Chen, Yubin Hu, Hailan Lin, Mingzhi Hao, Yan Zhou, Qizhong Chen, Zhangxian Chen

Abstract

Purpose: Unresectable intrahepatic cholangiocarcinoma (ICC) has a poor prognosis. The aim of this study was to evaluate the efficacy and safety of apatinib for patients with unresectable ICC.

Patients and methods: A total of 10 patients with unresectable ICC were enrolled for this single-center observational study between March 2, 2016, and August 27, 2019. Subjects received 500 mg apatinib on a daily basis. Tumor response was assessed by 1.1 response evaluation criteria in solid tumors. The progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. The drug-related adverse effects were also monitored.

Results: Based on the follow-up computed tomography and magnetic resonance imaging after treatment, 4 (40.0%), 4 (40.0%), and 2 (20.0%) patients achieved a partial response, stable disease, and progression of the disease, respectively. The response rate and disease control rate were 40.0% and 80.0%, respectively. The median PFS was 4.5 months (95% confidence interval: 3.157~5.843 months); the median OS was 6.5 months (95% confidence interval: 4.744~8.256 months). Furthermore, 3-, 6-, and 9-month OS rates were 77.5%, 61.7%, and 15.0%, respectively. The most common hematologic grade 3 adverse event was neutropenia (10%); the most common nonhematologic grade 3 adverse events were hypertension (20.0%) and hand-foot syndromes (20.0%). No treatment-related grade 4 or 5 adverse events were recorded.

Conclusion: Apatinib revealed to have antitumour activity in unresectable ICC patients, with manageable toxicities, and thus might be used as a new treatment option for patients with unresectable ICC.

Keywords: apatinib; efficacy; intrahepatic cholangiocarcinoma; safety; targeted therapy.

Conflict of interest statement

The authors report no conflicts of interest in this work.

© 2020 Hu et al.

Figures

Figure 1
Figure 1
Progression-free survival of apatinib in treatment of ICC.
Figure 2
Figure 2
Overall survival of apatinib in treatment of ICC.

References

    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7–34. doi:10.3322/caac.21551
    1. Bridgewater J, Galle PR, Khan SA, et al. Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. J Hepatol. 2014;60(6):1268–1289. doi:10.1016/j.jhep.2014.01.021
    1. Nakano M, Ariizumi SI, Yamamoto M. Intrahepatic cholangiocarcinoma. Semin Diagn Pathol. 2017;34(2):160–166. doi:10.1053/j.semdp.2016.12.012
    1. Saha SK, Zhu AX, Fuchs CS, Brooks GA. Forty-year trends in cholangiocarcinoma incidence in the U.S.: intrahepatic disease on the rise. Oncologist. 2016;21(5):594–599. doi:10.1634/theoncologist.2015-0446
    1. Patel T. Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States. Hepatology. 2001;33(6):1353–1357. doi:10.1053/jhep.2001.25087
    1. Massarweh NN, El-Serag HB. Epidemiology of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Cancer Control. 2017;24(3):1073274817729245. doi:10.1177/1073274817729245
    1. Chen WQ, Zheng RS, Baade PD, et al. Cancer statistics in china, 2015. CA Cancer J Clin. 2016;66(2):115–132. doi:10.3322/caac.21338
    1. Jong MCD, Nathan H, Sotiropoulos GC, et al. Intrahepatic cholangiocarcinoma: an international multi-institutional analysis of prognostic factors and lymph node assessment. J Clin Oncol. 2011;29(23):3140–3145. doi:10.1200/JCO.2011.35.6519
    1. Tan JCC, Coburn NG, Baxter NN, Kiss A, Law CHL. Surgical management of intrahepatic cholangiocarcinoma - a population-based study. Ann Surg Oncol. 2008;15(2):600–608. doi:10.1245/s10434-007-9627-x
    1. Nathan H, Pawlik TM, Wolfgang CL, Choti MA, Cameron JL, Schulick RD. Trends in survival after surgery for cholangiocarcinoma: a 30-year population-based SEER database analysis. J Gastrointest Surg. 2007;11(11):1488–1497. doi:10.1007/s11605-007-0282-0
    1. Ohtsuka M, Ito H, Kimura F, et al. Extended hepatic resection and outcomes in intrahepatic cholangiocarcinoma. J Hepatobiliary Pancreat Surg. 2003;10(4):259–264. doi:10.1007/s00534-002-0724-8
    1. Razumilava N, Gores GJ. Cholangiocarcinoma. Lancet. 2014;383(9935):2168–2179. doi:10.1016/S0140-6736(13)61903-0
    1. Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362(14):1273–1281. doi:10.1056/NEJMoa0908721
    1. Sahai V, Catalano PJ, Zalupski MM, et al. Nab-paclitaxel and gemcitabine as first-line treatment of advanced or metastatic cholangiocarcinoma: a phase 2 clinical trial. JAMA Oncol. 2018;4(12):1707–1712. doi:10.1001/jamaoncol.2018.3277
    1. Shroff RT, Javle MM, Xiao LC, et al. Gemcitabine, cisplatin, and nab-paclitaxel for the treatment of advanced biliary tract cancers: a phase 2 clinical trial. JAMA Oncol. 2019;5(6):824–830. doi:10.1001/jamaoncol.2019.0270
    1. Folkman J, Parris EE, Folkman J. Tumor angiogenesis: therapeutic implication. N Engl J Med. 1971;285(21):1182–1186. doi:10.1056/NEJM197111182852108
    1. Sia D, Tovar V, Moeini A, Llovet JM. Intrahepatic cholangiocarcinoma: pathogenesis and rationale for molecular therapies. Oncogene. 2013;32(41):4861–4870. doi:10.1038/onc.2012.617
    1. El-Khoueiry AB, Rankin CJ, Ben-Josef E, et al. SWOG 0514: a phase II study of sorafenib in patients with unresectable or metastatic gallbladder carcinoma and cholangiocarcinoma. Invest New Drugs. 2012;30(4):1646–1651. doi:10.1007/s10637-011-9719-0
    1. El-Khoueiry AB, Rankin C, Siegel AB, et al. S0941: a phase 2 SWOG study of sorafenib and erlotinib in patients with advanced gallbladder carcinoma or cholangiocarcinoma. Br J Cancer. 2014;110(4):882–887. doi:10.1038/bjc.2013.801
    1. Santoro A, Gebbia V, Pressiani T, et al. A randomized, multicenter, phase II study of vandetanib monotherapy versus vandetanib in combination with gemcitabine versus gemcitabine plus placebo in subjects with advanced biliary tract cancer: the VanGogh study. Ann Oncol. 2015;26(3):542–547. doi:10.1093/annonc/mdu576
    1. Yi JH, Thongprasert S, Lee J, et al. A phase II study of sunitinib as a second-line treatment in advanced biliary tract carcinoma: a multicentre, multinational study. Eur J Cancer. 2012;48(2):196–201. doi:10.1016/j.ejca.2011.11.017
    1. Li J, Qin SK, Xu JM, 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):1448–1454. doi:10.1200/JCO.2015.63.5995
    1. Song ZZ, Zhao LF, Zuo J, et al. 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;13:603–613. doi:10.2147/OTT.S222985
    1. Lan CY, Wang Y, Xiong Y, et al. Apatinib combined with oral etoposide in patients with platinum-resistant or platinum-refractory ovarian cancer (AEROC): a phase 2, single-arm, prospective study. Lancet Oncol. 2018;19(9):1239–1246. doi:10.1016/S1470-2045(18)30349-8
    1. Zhang YQ, Fan WZ, Wang Y, Huang GH, Li JP. Apatinib for patients with sorafenib-refractory advanced hepatitis B virus related hepatocellular carcinoma: results of a pilot study. Cancer Control. 2019;26(1):1073274819872216. doi:10.1177/1073274819872216
    1. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–247. doi:10.1016/j.ejca.2008.10.026
    1. Ji JH, Song HN, kim RB, et al. Natural history of metastatic biliary tract cancer (BTC) patients with good performance status (PS) who were treated with only best supportive care (BSC). Jpn J Clin Oncol. 2015;45(3):256–260. doi:10.1093/jjco/hyu210
    1. Park SY, Kim JH, Yoon HJ, Lee IS, Yoon HK, Kim KP. Transarterial chemoembolization versus supportive therapy in the palliative treatment of unresectable intrahepatic cholangiocarcinoma. Clin Radiol. 2011;66(4):322–328. doi:10.1016/j.crad.2010.11.002
    1. Liu Z, Chen JL, Fang Y, Xu FH, Pan HM, Han WD. The efficacy and safety of apatinib treatment for patients with unresectable or relapsed liver cancer: a retrospective study. J Cancer. 2018;9(16):2773–2777. doi:10.7150/jca.26376
    1. Nakeeb A, Tran KQ, Black MJ, et al. Improved survival in resected biliary malignancies. Surgery. 2002;132(4):555–564. doi:10.1067/msy.2002.127555
    1. Saxena A, Bester L, Chua TC, Chu FC, Morris DL. Yttrium-90 radiotherapy for unresectable intrahepatic cholangiocarcinoma: a preliminary assessment of this novel treatment option. Ann Surg Oncol. 2010;17(2):484–491. doi:10.1245/s10434-009-0777-x
    1. Hoffmann RT, Paprottka PM, Schön A, et al. Transarterial hepatic yttrium-90 radioembolization in patients with unresectable intrahepatic cholangiocarcinoma: factors associated with prolonged survival. Cardiovasc Intervent Radiol. 2012;35(1):105–116. doi:10.1007/s00270-011-0142-x
    1. Ma FC, Yu Q, Zeng ZM, et al. Progression-free survival of up to 8 months of an advanced intrahepatic cholangiocarcinoma patient treated with apatinib: a case report. Onco Targets Ther. 2017;10:5237–5242. doi:10.2147/OTT.S146051
    1. Valle JW, Lamarca A, Goyal L, Barriuso J, Zhu AX. New horizons for precision medicine in biliary tract cancers. Cancer Discov. 2017;7(9):943–962. doi:10.1158/-17-0245
    1. Saha SK, Gordan JD, Kleinstiver BP, et al. Isocitrate dehydrogenase mutations confer dasatinib hypersensitivity and SRC dependence in intrahepatic cholangiocarcinoma. Cancer Discov. 2016;6(7):727–739. doi:10.1158/-15-1442
    1. Javle M, Lowery M, Shroff RT, et al. Phase II study of BGJ398 in patients with FGFR-altered advanced cholangiocarcinoma. J Clin Oncol. 2018;36(3):276–282. doi:10.1200/JCO.2017.75.5009
    1. Borad MJ, Champion MD, Egan JB, et al. Integrated genomic characterization reveals novel, therapeutically relevant drug targets in FGFR and EGFR pathways in sporadic intrahepatic cholangiocarcinoma. PLoS Genet. 2014;10(2):e1004135. doi:10.1371/journal.pgen.1004135
    1. Bekaii-Saab T, Phelps MA, Li XB, et al. Multi-institutional phase II study of selumetinib in patients with metastatic biliary cancers. J Clin Oncol. 2011;29(17):2357–2363. doi:10.1200/JCO.2010.33.9473

Source: PubMed

3
구독하다