Cancer Management and Research Dovepress open access to scientific and medical research Open Access Full Text Article ORIGINAL RESEARCH Large Scale, Multicenter, Prospective Study of Apatinib in Advanced Gastric Cancer: A Real-World Study from China This article was published in the following Dove Press journal: Cancer Management and Research 1, 2, 3, Wanren Peng, * Fenglin Zhang, * Zishu Wang, * Background: In China, gastric cancer (GC) ranks second in incidence and mortality. Over Dongliang Li, 4,*YifuHe,5,* Zhongliang Ning,6 Lili Sheng,7 Jidong Wang,8 Xiaoyang Xia,9 80% of patients with GC were diagnosed at an advanced stage with poor clinical outcome. Changjun Yu,10 Zian Wang,3 Yo n g Z h ao, 11 12 13 14 Chemotherapy was the mainstream treatment with limited benefit. Apatinib, an inhibitor of Hui Liang, Bing Hu, Cuiling Sun, Daoqin Wang,15 Yunsheng Cheng,16 Ming Pan,17 targeting vascular endothelial growth factor receptor 2 (VEGFR2), has been approved for Liming Xia,18 Xinglai Guo,19 Yanshun Zhang,20 Zhiqiang Hu,21 Xinzhong Li,22 Lin Lu,23 Jun Zhang,24 third-line treatment of advanced gastric cancer. However, the data of apatinib treatment in the Hong Qian,8 Hua Xie,25 Guoping Sun1,* real-world setting are limited. In this real-world study, we aimed to understand the current 1Department of Oncology, The First Affiliated Hospital of treatment pattern of apatinib, investigate the effectiveness and safety of apatinib in real-world Anhui Medical University, Hefei, Anhui 230022, People’s Republic of China; 2Department of Oncology, People’s settings, and explore the potential factors associated with the clinical outcomes. Hospital of Maanshan City, Maanshan, Anhui 243000, People’s Republic of China; 3Department of Oncology, The Methods: This was a prospective, multicenter observational study in a real-world setting. First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, People’sRepublicofChina;4Department of Patients aged ≥18 years with histologic diagnosis of advanced GC were eligible for enroll- Gastrointestinal Surgery, People’sHospitalofLu’an City, Lu’an, Anhui 237005, People’s Republic of China; ment. The eligible patients received either apatinib monotherapy or apatinib plus chemother- 5Department of Oncology, The First Affiliated Hospital of University of Science and Technology of China (Anhui apy by physician’s discretion. Apatinib treatment could be used as first-line, second-line, or Provincial Cancer Hospital), Hefei, Anhui 230022, People’s Republic of China; 6Department of Gastrointestinal third-line and above therapy. The primary endpoint was progression-free survival (PFS). The Surgery, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Cancer secondary endpoints were overall survival (OS), ORR, DCR, and safety profile. Hospital), Hefei, Anhui 230022, People’s Republic of China; 7Department of Oncology, Yijishan Hospital of WanNan Results: A total of 737 patients with advanced gastric cancer treated with apatinib were Medical College, Wuhu, Anhui 340202, People’sRepublicof China; 8Department of Oncology, The Navy Anqing included in the FAS population. A total of 54.9% patients used apatinib monotherapy and Hospital, Anqing, Anhui 246003, People’sRepublicofChina; 9Department of Oncology, The First People’sHospitalof 45.1% patients used apatinib combination therapy. A total of 44.1% patients received Chuzhou City, Chuzhou, Anhui 239000, People’sRepublic of China; 10Department of Gastrointestinal Surgery, The apatinib in first-line treatment, 28.2% in second-line, and 27.7% in third-line and above. In First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, People’s Republic of China; 11Department of first-line treatment, the objective response rate (ORR) was 9.09% and 16.42% in apatinib Oncology, People’s Hospital of Lu’an City, Lu’an, Anhui 237005, People’s Republic of China; 12Department of monotherapy and combination therapy groups, and disease control rate (DCR) was 78.41% Oncology, Lu’an Hospital of Traditional Chinese Medicine, Lu’an, Anhui 237006, People’s Republic of China; and 89.29%, respectively. Patients who received combination therapy achieved significantly 13Department of Oncology, The First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui longer median progression-free survival (mPFS; 6.18 vs 3.52 months, p<0.01) and median 230022, People’s Republic of China; 14Department of Oncology, People’s Hospital of Fuyang City, Fuyang, Anhui overall survival (mOS; 8.72 vs 5.92 months, p<0.01) compared with monotherapy. In 236047, People’s Republic of China; 15Department of Gastrointestinal Surgery, Wanbei Coal-Electricity Group second-line and third-line therapy, combination therapy showed a better trend in tumor General Hospital, Suzhou, Anhui 234000, People’sRepublic of China; 16Department of Oncology, The Second Affiliated response and survival outcomes compared with monotherapy. For all patients, apatinib Hospital of Anhui Medical University, Hefei, Anhui 230601, People’s Republic of China; 17Department of Oncology, combined with paclitaxel were associated with longer mPFS compared with other combina- People’s Hospital of Chizhou City, Chizhou, Anhui 247000, People’s Republic of China; 18Department of Oncology,The tions (8.88 vs 6.62 months). Multivariate analysis showed that combination with paclitaxel First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230031, People’sRepublicofChina; (p=0.02) and experience of apatinib-related specific AEs (p<0.01) were independent pre- 19Department of Oncology, Fuyang Cancer Hospital, Fuyang, Anhui 236033, People’s Republic of China; dictors for PFS and OS. The safety profile was tolerable and no unexpected adverse events 20Department of Oncology, Huainan First People’s Hospital, Huainan, Anhui 232000, People’sRepublicof were reported. China; 21Department of Oncology, Huaibei Miners General Hospital, Huaibei, Anhui 235000, People’s Republic of China; 22Department of Oncology, People’s Hospital of Conclusion: In a real-world setting, apatinib showed a favorable effectiveness and safety Huaibei, Huaibei, Anhui 235000, People’s Republic of China; fi 23Department of Oncology, The 901 Hospital of the Joint pro le in patients with advanced gastric cancer. Apatinib combination therapy, especially Logistic Support Force of the People’s Liberation Army of fi fi China, Hefei, Anhui 230033, People’s Republic of China; combined with paclitaxel, might lead to better survival bene tin rst-line treatment. 24Department of Oncology, The Second People’s Hospital fi of Wuhu, Wuhu, Anhui 241001, People’s Republic of China; Combination with paclitaxel and the occurrence of apatinib-speci c AEs were independent 25Department of Oncology, The People’sHospitalof Xuancheng City, Xuancheng, Anhui 242000, People’s factors associated with better survival outcomes. Republic of China Trial Registration: NCT03333967. *These authors contributed equally to this work Keywords: apatinib, combination therapy, real-world, advanced gastric cancer Correspondence: Guoping Sun Email [email protected] submit your manuscript | www.dovepress.com Cancer Management and Research 2020:12 6977–6985 6977 DovePress © 2020 Peng et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php – http://doi.org/10.2147/CMAR.S249153 and incorporate the Creative Commons Attribution Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). Peng et al Dovepress Introduction contraindication for apatinib, they were not enrolled in Gastric cancer (GC) is one of the most common malignant the current study. In addition, the patients who were not tumors and the third leading cause of cancer-related deaths eligible for this study according to the physician’s discre- worldwide.1 In China, GC ranks second in incidence and tion were not enrolled in this study. mortality.2–5 Over 80% of patients with GC are diagnosed at an advanced stage with poor clinical outcome and a low Study Design and Treatment 5-year survival rate of <20%.6,7 Chemotherapy is the This was a prospective, multicenter observational study in recommended treatment in China but the benefits are lim- a real-world setting. The eligible patients received apatinib ited. Consequently, it is crucial to explore and optimize monotherapy or apatinib plus chemotherapy. The che- treatment strategy to improve the survival benefitof motherapy regimens included docetaxel, paclitaxel, cape- fl patients with GC. citabine and oxaliplatin (XELOX), 5- uorouracil (5-Fu), In recent years, anti-angiogenic therapy has become a epirubicin+oxaliplatin+capecitabine (EOX), docetaxel fl ’ main treatment choice for cancer patients, and some angio- +cisplatin+ uorouracil (DCF). Based on physician s dis- ’ genesis inhibitors have shown favorable efficacy in lung, cretion and patients approval, apatinib could be used as fi breast, colon and gastric cancers.8,9 Apatinib is a small- rst-line, second-line, or third-line and above therapy. molecule tyrosine kinase inhibitor (TKI) that highly selec- Apatinib was administered (250