Browse > Article
http://dx.doi.org/10.5230/jgc.2022.22.e33

Apatinib as a Third-Line Treatment for HER2-Positive Metastatic Gastric Cancer: A Multi-Center Single-Arm Cohort Study  

Zhang, Xin (Department of General Surgery, Handan Central Hospital)
Huo, Haoran (Department of General Surgery, Handan Central Hospital)
Nie, Yanan (Endoscopy Room, Han Gang Hospital)
Xue, Jiadong (Department of General Surgery, Handan Central Hospital)
Yuan, Zengjiang (Department of General Surgery, Handan Central Hospital)
Zhang, Zhenyi (Department of General Surgery, Handan Central Hospital)
Publication Information
Journal of Gastric Cancer / v.22, no.4, 2022 , pp. 408-417 More about this Journal
Abstract
Purpose: Treatment options are limited after the failure of first-and second-line treatments in patients with HER2+ metastatic gastric cancer (mGC). The present study aimed to explore the efficacy, safety, and prognostic factors of apatinib efficacy as a third-line therapy for patients with human epithelial growth factor receptor 2-positive (HER2+) mGC. Materials and Methods: A total of 59 HER2+ mGC patients who received apatinib as third-line therapy were retrospectively enrolled in this two-center, single-arm, cohort study; the clinical response, survival data, and adverse events were retrieved. Results: The median progression-free survival (PFS) was 5.2 months (95% confidence interval [CI], 3.9-6.5), and the median overall survival (OS) was 8.2 months (95% CI, 6.6-9.8) Furthermore, forward stepwise multivariate Cox regression analysis showed that a higher Eastern Cooperative Oncology Group performance status score and multiple metastases were independently correlated with decreased PFS and OS (both P<0.05). The main adverse events were leukopenia (45.8%), hypertension (44.1%), thrombocytopenia (39.0%), hand-foot syndrome (37.3%), and elevated transaminase (33.9%). Grade 3 adverse events mainly included hypertension (5.1%) and neutropenia (5.1%); grade 4 adverse events did not occur. Conclusions: Apatinib is efficient and well tolerated in patients with HER2+ mGC as a third-line treatment, suggesting that it may be a candidate of choice for these patients.
Keywords
Apatinib; Gastric cancer; Prognosis; Mortality; Safety;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Li J, Qin S, Xu J, Guo W, Xiong J, Bai Y, et al. Apatinib for chemotherapy-refractory advanced metastatic gastric cancer: results from a randomized, placebo-controlled, parallel-arm, phase II trial. J Clin Oncol 2013;31:3219-3225.   DOI
2 Meulendijks D, Beerepoot LV, Boot H, de Groot JW, Los M, Boers JE, et al. Trastuzumab and bevacizumab combined with docetaxel, oxaliplatin and capecitabine as first-line treatment of advanced HER2-positive gastric cancer: a multicenter phase II study. Invest New Drugs 2016;34:119-128.   DOI
3 Li J, Qin S, Xu J, Xiong J, Wu C, Bai Y, 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;34:1448-1454.   DOI
4 Kawamoto Y, Yuki S, Meguro T, Hatanaka K, Uebayashi M, Nakamura M, et al. Phase II study of continued trastuzumab plus irinotecan in patients with HER2-positive gastric cancer previously treated with trastuzumab (HGCSG 1201). Oncologist 2022;27:340-e374.   DOI
5 Kim BJ, Jee HJ, Rha SY, Han HS, Ryu MH, Park SH, et al. Ramucirumab plus paclitaxel as a second-line treatment in HER2-positive gastric cancer: subgroup analysis of a nationwide, real-world study in Korea (KCSG-ST19-16). Gastric Cancer 2022;25:609-618.   DOI
6 Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-247.   DOI
7 Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424.   DOI
8 Machlowska J, Baj J, Sitarz M, Maciejewski R, Sitarz R. Gastric cancer: epidemiology, risk factors, classification, genomic characteristics and treatment strategies. Int J Mol Sci 2020;21:4012.   DOI
9 Shah SC, Canakis A, Peek RM Jr, Saumoy M. Endoscopy for gastric cancer screening is cost effective for Asian Americans in the United States. Clin Gastroenterol Hepatol 2020;18:3026-3039.   DOI
10 Satoh T, Xu RH, Chung HC, Sun GP, Doi T, Xu JM, et al. Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in Asian populations: TyTAN--a randomized, phase III study. J Clin Oncol 2014;32:2039-2049.   DOI
11 Yoshioka T, Takahashi M, Sakamoto Y, Okita A, Fukui T, Murakawa Y, et al. Cisplatin plus capecitabine after adjuvant S-1 in metastatic gastric cancer: a phase II T-CORE1102 trial. Anticancer Res 2022;42:2009-2015.   DOI
12 Sakai D, Omori T, Fumita S, Fujita J, Kawabata R, Matsuyama J, et al. Real-world effectiveness of third- or later-line treatment in Japanese patients with HER2-positive, unresectable, recurrent or metastatic gastric cancer: a retrospective observational study. Int J Clin Oncol 2022;27:1154-1163.   DOI
13 Ajani JA, D'Amico TA, Almhanna K, Bentrem DJ, Chao J, Das P, et al. Gastric cancer, version 3.2016, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2016;14:1286-1312.   DOI
14 Wagner AD, Grothe W, Haerting J, Kleber G, Grothey A, Fleig WE. Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. J Clin Oncol 2006;24:2903-2909.   DOI
15 Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, et al. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastrooesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol 2017;18:640-653.   DOI
16 Hecht JR, Bang YJ, Qin SK, Chung HC, Xu JM, Park JO, et al. Lapatinib in combination with capecitabine plus oxaliplatin in human epidermal growth factor receptor 2-positive advanced or metastatic gastric, esophageal, or gastroesophageal adenocarcinoma: TRIO-013/LOGiC--A randomized phase III trial. J Clin Oncol 2016;34:443-451.
17 Roviello G, Catalano M, D'Angelo A, Palmieri VE. Second line of treatment for HER2-positive gastric cancer: an evolving issue. Rep Pract Oncol Radiother 2021;26:316-317.   DOI
18 Kong F, Yao Y, Deng R, Li X, Jia Y. Hopes and failures in front-line advanced HER2-positive gastric cancer therapy. Anticancer Drugs 2021;32:675-680.   DOI
19 Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, et al. Trastuzumab deruxtecan in previously treated HER2-positive gastric cancer. N Engl J Med 2020;382:2419-2430.   DOI
20 Roviello G, Ravelli A, Fiaschi AI, Cappelletti MR, Gobbi A, Senti C, et al. Apatinib for the treatment of gastric cancer. Expert Rev Gastroenterol Hepatol 2016;10:887-892.
21 Satoh T, Kang YK, Chao Y, Ryu MH, Kato K, Cheol Chung H, et al. Exploratory subgroup analysis of patients with prior trastuzumab use in the ATTRACTION-2 trial: a randomized phase III clinical trial investigating the efficacy and safety of nivolumab in patients with advanced gastric/gastroesophageal junction cancer. Gastric Cancer 2020;23:143-153.   DOI
22 Jomrich G, Schoppmann SF. Targeting HER 2 and angiogenesis in gastric cancer. Expert Rev Anticancer Ther 2016;16:111-122.   DOI
23 Jung YD, Mansfield PF, Akagi M, Takeda A, Liu W, Bucana CD, et al. Effects of combination anti-vascular endothelial growth factor receptor and anti-epidermal growth factor receptor therapies on the growth of gastric cancer in a nude mouse model. Eur J Cancer 2002;38:1133-1140.   DOI
24 Shao F, Zhang H, Yang X, Luo X, Liu J. Adverse events and management of apatinib in patients with advanced or metastatic cancers: a review. Neoplasma 2020;67:715-723.   DOI
25 Fathi Maroufi N, Rashidi MR, Vahedian V, Akbarzadeh M, Fattahi A, Nouri M. Therapeutic potentials of Apatinib in cancer treatment: possible mechanisms and clinical relevance. Life Sci 2020;241:117106.   DOI
26 Smyth EC, Nilsson M, Grabsch HI, van Grieken NC, Lordick F. Gastric cancer. Lancet 2020;396:635-648.   DOI
27 Wang FH, Zhang XT, Li YF, Tang L, Qu XJ, Ying JE, et al. The Chinese Society of Clinical Oncology (CSCO): clinical guidelines for the diagnosis and treatment of gastric cancer, 2021. Cancer Commun (Lond) 2021;41:747-795.   DOI
28 Arslan C, Atilla FD. Modified docetaxel, cisplatin, and 5-fluorouracil combination regimen and capecitabine maintenance in metastatic gastric cancer: toxicity and efficacy results. Support Care Cancer 2022;30:4447-4455.   DOI
29 Xue JM, Astere M, Zhong MX, Lin H, Shen J, Zhu YX. Efficacy and safety of apatinib treatment for gastric cancer, hepatocellular carcinoma and non-small cell lung cancer: a meta-analysis. Onco Targets Ther 2018;11:6119-6128.   DOI
30 Li H, Huang H, Zhang T, Feng H, Wang S, Zhang Y, et al. Apatinib: A novel antiangiogenic drug in monotherapy or combination immunotherapy for digestive system malignancies. Front Immunol 2022;13:937307.   DOI
31 Yu GC, Yang J, Ye B, Xu LL, Li XY, Zheng GR. Apatinib in the treatment of advanced non-small-cell lung cancer: a meta-analysis. Math Biosci Eng 2019;16:7659-7670.   DOI