Salvage treatment with apatinib for advanced non-small-cell lung cancer

Zhengbo Song, Xinmin Yu, Guangyuan Lou, Xun Shi, Yiping Zhang, Zhengbo Song, Xinmin Yu, Guangyuan Lou, Xun Shi, Yiping Zhang

Abstract

Objective: No definitive chemotherapeutic regimen has been established in patients with non-small-cell lung cancer (NSCLC) who failed second- or third-line treatment. The aim of this study was to evaluate apatinib, a VEGFR-2 inhibitor, in advanced NSCLC as salvage treatment.

Methods: We evaluated the efficacy and toxicity of apatinib in patients with previously treated advanced NSCLC from 2014 to 2015 in Zhejiang Cancer Hospital. Survival analysis was performed by the Kaplan-Meier method.

Results: Forty-two patients were included in the present study. Four patients achieved partial response, and 22 achieved stable disease, representing a response rate of 9.5% and a disease control rate of 61.9%. Median progression-free survival and overall survival were 4.2 and 6.0 months, respectively. The toxicities associated with apatinib were generally acceptable with a total grade 3/4 toxicity of 50%.

Conclusion: Apatinib appears to have some activity against advanced NSCLC when utilized as salvage treatment.

Keywords: VEGF; apatinib; efficacy; non-small-cell lung cancer.

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Kaplan–Meier estimates of progression-free survival of apatinib treatment.
Figure 2
Figure 2
Kaplan–Meier estimates of overall survival of apatinib treatment.

References

    1. Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115–132.
    1. Mitsudomi T, Morita S, Yatabe Y, et al. West Japan Oncology Group Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 2010;11(2):121–128.
    1. Zhou C, Wu YL, Chen G, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011;12(8):735–742.
    1. Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361:947–957.
    1. Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013;368(25):2385–2394.
    1. Song Z, Zhang Y. Retreatment with pemetrexed chemotherapy in advanced non-small cell lung cancer patient. J Thorac Dis. 2014;6:856–860.
    1. Garon EB, Ciuleanu TE, Arrieta O, et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet. 2014;384(9944):665–673.
    1. Hall RD, Le TM, Haggstrom DE, Gentzler RD. Angiogenesis inhibition as a therapeutic strategy in non-small cell lung cancer (NSCLC) Transl Lung Cancer Res. 2015;4:515–523.
    1. Hanrahan EO, Heymach JV. Vascular endothelial growth factor receptor tyrosine kinase inhibitors vandetanib (ZD6474) and AZD2171 in lung cancer. Clin Cancer Res. 2007;13(15 pt 2):s4617–s4622.
    1. Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006;355(24):2542–2550.
    1. Reck M, von Pawel J, Zatloukal P, et al. Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. J Clin Oncol. 2009;27(8):1227–1234.
    1. Scott AJ, Messersmith WA, Jimeno A. Apatinib: a promising oral antiangiogenic agent in the treatment of multiple solid tumors. Drugs Today (Barc) 2015;51(4):223–229.
    1. Li J, Qin S, Xu J, 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(26):3219–3225.
    1. Li J, Qin S, Xu J, 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.
    1. Zhang K, Shi M, Huang C, et al. A phase II, multicenter, placebo-controlled trial of apatinib in patients with advanced nonsquamous non-small cell lung cancer (NSCLC) after two previous treatment regimens. J Clin Oncol. 2010;15(suppl):7548.
    1. Sun JM, Lee KW, Kim JH, et al. Efficacy and toxicity of pemetrexed as a third-line treatment for non-small cell lung cancer. Jpn J Clin Oncol. 2008;39:27–32.
    1. Girard N, Jacoulet P, Gainet M, et al. Third-line chemotherapy in advanced non-small cell lung cancer: identifying the candidates for routine practice. J Thorac Oncol. 2009;4(12):1544–1549.
    1. Ding J, Chen X, Gao Z, et al. Metabolism and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor apatinib in humans. Drug Metab Dispos. 2013;41:1195–1210.
    1. Aziz MA, Serya RA, Lasheen DS, et al. Discovery of potent VEGFR-2 inhibitors based on furopyrimidine and thienopyrimidne scaffolds as cancer targeting agents. Sci Rep. 2016;6:24460.
    1. Zhang HQ, Gong FH, Li CG, et al. Design and discovery of 4-anilinoquinazoline-acylamino derivatives as EGFR and VEGFR-2 dual TK inhibitors. Eur J Med Chem. 2016;109:371–379.
    1. Ghavamipour F, Shahangian SS, Sajedi RH, Arab SS, Mansouri K, Aghamaali MR. Development of a highly-potent anti-angiogenic VEGF8-109 heterodimer by directed blocking of its VEGFR-2 binding site. FEBS J. 2014;281(19):4479–4494.
    1. Hu X, Zhang J, Xu B, et al. Multicenter phase II study of apatinib, a novel VEGFR inhibitor in heavily pretreated patients with metastatic triple-negative breast cancer. Int J Cancer. 2014;135(8):1961–1969.
    1. Ding L, Li QJ, You KY, Jiang ZM, Yao HR. The use of apatinib in treating nonsmall-cell lung cancer: case report and review of literature. Medicine (Baltimore) 2016;95(20):e3598.
    1. Shepherd FA, Dancey J, Ramlau R, et al. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol. 2000;18(10):2095–2103.
    1. Seto T, Kato T, Nishio M, et al. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol. 2014;15(11):1236–1244.

Source: PubMed

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