Efficacy and safety of apatinib for the treatment of AFP-producing gastric cancer

Ningning Li, Chunmei Bai, Ruixing Zhang, Liwen Ma, Xiubao Ren, Junping Zhang, Zhanzhao Fu, Lin Zhao, Ningning Li, Chunmei Bai, Ruixing Zhang, Liwen Ma, Xiubao Ren, Junping Zhang, Zhanzhao Fu, Lin Zhao

Abstract

Background: Alpha-fetoprotein-producing gastric cancer (AFPGC) poses a therapeutic challenge worldwide because of its poor prognosis. This study aimed to evaluate the efficacy and safety of antiangiogenic drug apatinib in advanced AFPGC in a real-world setting.

Methods: From September 2015 to December 2017, twenty-one patients identified with AFPGC from the clinical trial AHEAD-G202, an open-label, prospective, multicenter, non-interventional study of apatinib for advanced metastatic gastric cancer, were enrolled to perform this analysis. Patients received oral apatinib as monotherapy or combination therapy. A treatment cycle was defined as 28 days. The primary outcome was progression-free survival (PFS) and overall survival (OS), and the secondary outcomes included safety, objective response rate (ORR), and disease control rate (DCR).

Results: Twenty patients were evaluated for the apatinib efficacy analysis. The ORR of apatinib was 10%, whereas the DCR was 70%. The median PFS was 3.5 months [95%confidence interval (CI): 2.34-4.66]. The median OS was 4.5 months (95%CI: 3.49-5.51). Median OS of AFPGC patients without carcinoembryonic antigen (CEA) elevation achieved 30.8 months. CEA elevation was considered to be a potential independent predictive factor for OS (P = 0.030) and PFS (P = 0.047) by the analysis of multivariate analysis. The most common grade 3 to 4 adverse events (AEs) were hypertension (4.8%), hand-foot syndrome (4.8%), anorexia (4.8%), and vomiting and nausea (4.8%).

Conclusion: Apatinib showed promising efficacy and an acceptable safety profile in patients with advanced AFPGC. Antiangiogenic therapy may be a good strategy for the treatment of AFPGC as a rare sub-type of gastric cancer.

Trial registration: AHEAD-G202 (NCT02668380).

Keywords: AFP-producing gastric cancer; Alpha-fetoprotein; Apatinib; Target therapy.

Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Copyright © 2020. Published by Elsevier Inc.

Figures

Fig. 1
Fig. 1
Kaplan-Meier estimates of progression-free survival (PFS) (A) and overall survival (OS) (B) of 21 patients with AFPGC. (A) Median PFS was 3.5 months with apatinib. (B) Median OS was 4.5 months with apatinib.
Fig. 2
Fig. 2
Kaplan-Meier estimates of progression-free survival (PFS) for different factors. (A) PFS of patients with normal CEA level and those with elevated CEA level (P = 0.029). (B) PFS of patients with grades 3 or 4 AEs and those without grades 3 or 4 AEs (P = 0.013).
Fig. 3
Fig. 3
Overall survival (OS) of patients with normal CEA level and those with elevated CEA level (P = 0.017).

References

    1. Bergstrand C.G., Czar B. Demonstration of a new protein fraction in serum from the human fetus. Scand. J. Clin. Lab. Invest. 1956;8:174–179.
    1. Metzgeroth G., Strobel P., Baumbusch T., Reiter A., Hastka J. Hepatoid adenocarcinoma -review of the literature illustrated by a rare case originating in the peritoneal cavity. Onkologie. 2010;33:263–269.
    1. Yamagata T., Yamagata Y., Nakanishi M., Matsunaga K., Minakata Y., Ichinose M. A case of primary lung cancer producing alpha-fetoprotein. Can. Respir. J. 2004;11:504–506.
    1. Matsueda K., Yamamoto H., Yoshida Y., Notohara K. Hepatoid carcinoma of the pancreas producing protein induced by vitamin K absence or antagonist II (PIVKA-II) and alpha-fetoprotein (AFP) J. Gastroenterol. 2006;41:1011–1019.
    1. Kinjo T., Taniguchi H., Kushima R., Sekine S., Oda I., Saka M., Gotoda T., Kinjo F., Fujita J., Shimoda T. Histologic and immunohistochemical analyses of α -fetoprotein-producing cancer of the stomach. Am. J. Surg. Pathol. 2012;36:56–65.
    1. Cappetta A., Bergamo F., Mescoli C., Lonardi S., Rugge M., Zagonel V. Hepatoid adenocarcinoma of the colon: what should we target? Pathol. Oncol. Res. 2012;18:93–96.
    1. Isonishi S., Ogura A., Kiyokawa T., Suzuki M., Kunito S., Hirama M., Tachibana T., Ochiai K., Tanaka T. Alpha-fetoprotein (AFP)-producing ovarian tumor in an elderly woman. Int. J. Clin. Oncol. 2009;14:70–73.
    1. Bourreille J., Metayer P., Sauger F., Matray F., Fondimare A. Existence of alpha feto protein during gastric-origin secondary cancer of the liver. Presse Med. 1970;78:1277–1278. (in French)
    1. Ishikura H., Fukasawa Y., Ogasawara K., Natori T., Tsukada Y., Aizawa M. An AFP-producing gastric carcinoma with features of hepatic differentiation. A case report. Cancer. 1985;56:840–848.
    1. Liu X., Cheng Y., Sheng W., Lu H., Xu Y., Long Z., Zhu H., Wang Y. Clinicopathologic features and prognostic factors in alpha-fetoprotein-producing gastric cancers: analysis of 104 cases. J. Surg. Oncol. 2010;102:249–255.
    1. Roviello G., Ravelli A., Polom K. Apatinib: a novel receptor tyrosine kinase inhibitor for the treatment of gastric cancer. Cancer Lett. 2016;372(2):187–191.
    1. McIntire K.R., Waldmann T.A., Moertel C.G., Go V.L. Serum alpha-fetoprotein in patients with neoplasms of the gastroin- testinal tract. Cancer Res. 1975;35:991–996.
    1. Chang Y.C., Nagasue N., Abe S., Taniura H., Kumar D.D., Nakamura T. Comparison between the clinicopathologic features of AFP-positive and AFP-negative gastric cancers. Am. J. Gastroenterol. 1992;87:321–325.
    1. Li Xiao-Dong, Wu Chang-Ping, Ji Mei. Characteristic analysis of α-fetoprotein-producing gastric carcinoma in China. World J. Surg. Oncol. 2013;11:246.
    1. Shibata Y., Sato K., Kodama M., Nanjyo H. Alpha-fetoprotein-producing early gastric cancer of the remnant stomach: report of a case. Surg. Today. 2007;37:995–999.
    1. Vivekanandarajah A., Atallah J.P., Gupta S. Alpha-fetoproteinproducing nonmetastatic gastric adenocarcinoma: a rare entity. J. Gastrointest. Cancer. 2014;45:225–227.
    1. Talamonti M.S., Kim S.P., Yao K.A., Wayne J.D., Feinglass J., Bennett C.L., Rao S. Surgical outcomes of patients with gastric carcinoma: the importance of primary tumor location and microvessel invasion. Surgery. 2003;134:720–727. discussion 727-729.
    1. Qu B.G., Bi W.M., Qu B.T., Qu T., Han X.H., Wang H., Liu Y.X., Jia Y.G. PRISMA-compliant article: clinical characteristics and factors influencing prognosis of patients with hepatoid adenocarcinoma of the stomach in China. Medicine (Baltimore). 2016;95:e3399.
    1. Bozkaya Y., Demirci N.S., Kurtipek A. Clinicopathological and prognostic characteristics in patients with AFP-secreting gastric carcinoma. Mol. Clin. Oncol. 2017 Aug;7(2):267–274.
    1. Shibata Y., Sato K., Kodama M., Nanjyo H. Alphafetoprotein-producing early gastric cancer of the remnant stomach: report of a case. Surg. Today. 2007;37:995–999.
    1. Nagai E., Ueyama T., Yao T., Tsuneyoshi M. Hepatoid adenocarcinoma of the stomach. CancerCancer. 1993;72:1827–1835.
    1. Yoshioka M., Inoue N., Someda H., Noguchi M., Sawada M., Azuma K. [A case of AFP-producing gastric cancer resected after efficient S-1/CDDP combination chemotherapy] Gan To Kagaku Ryoho. 2011 Jan;38(1) 105e8.
    1. Fukuda K., Ito S., Shimizu K., Mikami E., Sakuraba S., Shiroki T. [Retrospective analysis concerning AFP-producing gastric cancer] Gan To Kagaku Ryoho. 2013 Feb;40(2):191e5.
    1. Kunoki N., Nishiyama R., Ryuzaki H., Oonishi M., Yamamoto T., Uno A. A case of alpha-fetoprotein-producing gastric cancer with hepatic metastasis successfully treated with combination chemotherapy. Nihon Shokakibyo Gakkai Zasshi. 2008 Oct;105(10):1489e95.
    1. Wang Ya-Kun, Shen Lin, Jiao Xi. Predictive and prognostic value of serum AFP level and its dynamic changes in advanced gastric cancer patients with elevated serum AFP. World J. Gastroenterol. 2018;24(2):266–273.
    1. Baek S.K., Han S.W., DY O., Im S.A., Kim T.Y., Bang Y.J. Clinicopathologic characteristics and treatment outcomes of hepatoid adenocarcinoma of the stomach, a rare but unique subtype of gastric cancer. BMC Gastroenterol. 2011;11(1):56.
    1. Hirao K., Hirasaki S., Tsuzuki T., Kajiwara T., Hyodo I. Unresectable alpha fetoprotein-producing gastric cancer successfully treated with irinotecan and mitomycin C after S-1 failure. Intern. Med. 2004;43(2):106e10.
    1. Li Wei, Li Qian, Yu Yiyi. Effect of immune checkpoint inhibitors plus chemotherapy on advanced gastric cancer patients with elevated serum AFP or hepatoid adenocarcinoma. Cancer Manag. Res. 2020;12:11113–11119.
    1. Kamei S., Kono K., Amemiya H. Evaluation of VEGF and VEGF-C expression in gastric cancer cells producing alpha-fetoprotein. J. Gastroenterol. 2003;38:540–547.
    1. Yonemura Y., Endo Y., Fujita H. Role of vascular endothelial growth factor C expression in the development of lymph node metastasis in gastric cancer. Clin. Cancer Res. 1999;5:1823–1829.
    1. Yasuhiro A., Miho T., keisuke A.I.B.A., al et. Significant response to ramucirumab monotherapy in chemotherapy-resistant recurrent alpha‑fetoprotein-producing gastric cancer: a case report. Oncol. Lett. 2017;14:3039–3042.
    1. Koneri K., Hirono Y., Fujimoto D., Sawai K., Morikawa M., Murakami M., Goi T., Iida A., Katayama K., Yamaguchi A. Five-year survival of alpha-fetoprotein-producing gastric cancer with synchronous liver metastasis: a case report. J. Gastric Cancer. 2013;13:58–64.
    1. Fang Y.U., Wang L., Yang N., Gong X., Zhang Y.U., Qin S. Successful multimodal therapy for an α-fetoprotein-producing gastric cancer patient with simultaneous liver metastases. Oncol. Lett. 2015;10:3021–3025.
    1. Li J., Qin S., Xu J. 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.
    1. Li J., Qin S., Xu J. 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.
    1. Zhang Yong, Han Chun, Li Juan. Efficacy and safety for Apatinib treatment in advanced gastric cancer: a real world study. Sci Rep. 2017;7(1):13208. doi: 10.1038/s41598-017-13192-8.
    1. Zhu X.R., Zhu M.L., Wang Q. A case report of targeted therapy with apatinib in a patient with advanced gastric cancer and high serum level of alpha-fetoprotein. Medicine (Baltimore) 2016;95(37) article e4610.
    1. He Ruji, Yang Qinyi, Dong Xuqiang. Clinicopathologic and prognostic characteristics of alpha-fetoprotein–producing gastric cancer. Oncotarget. 2017;8(14):23817–23830.
    1. Sun W., Liu Y., Shou D., Sun Q., Shi J., Chen L., Liang T., Gong W. AFP (alpha fetoprotein): who are you in gastrology? Cancer Lett. 2015;357:43–46.
    1. Yakun Wang, Lin Shen, Xiaotian Zhang. The prognosis and clinicopathological characteristics of 70 gastric cancer patients with elevated serum AFP. Chin. J. Oncol. 2017;39(7)
    1. Kim J.H., Jun K.H., Jung H., Park I.S., Chin H.M. Prognostic value of preoperative serum levels of five tumor markers (carcinoembryonic antigen, CA19-9, alpha-fetoprotein, CA72-4, and CA125) in gastric cancer. Hepatogastroenterology. 2014;61:863–869.

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