Clinical research of intercalated combination of osimertinib and docetaxel in T790M mutationpositive lung adenocarcinoma patients with bone metastasis in the southern Hainan Province

Abstract

Abstract:ObjectiveTo study the clinical application of intercalated combination of osimertinib and docetaxel in T790M mutationpositive lung adenocarcinoma patients with bone metastasis in the southern Hainan Province. MethodsT790M mutationpositive lung adenocarcinoma patients with bone metastasis in the southern Hainan Province treated at the Third People′s Hospital of Hainan Province from January 2018 to October 2018 were enrolled, and they were divided into intercalated combination of osimertinib and docetaxel group (n=32) and osimertinib group (n=28) according to the treatment. The patients in intercalated combination of osimertinib and docetaxel group received oral osimertinib (80 mg, qd), and received docetaxel (75 mg/m2, repeated in threeweek intervals) when taking to tumor progression, and oral osimertinib treatment (80 mg, qd) was maintained until tumor partial response or stable disease after chemotherapy. The patients in osimertinib group received oral osimertinib (80 mg, qd). The patients in both groups received zoledronic acid. The response rate, disease control rate, overall survival (OS) and the incidence of adverse reactions of both groups were contrastively analyzed. ResultsThe response rate of intercalated combination of osimertinib and docetaxel group (62.5%, 20/32) was higher than that of osimertinib group (35.7%, 10/28), and disease control rate (93.8%, 30/32) was also higher than that of osimertinib group (67.9%, 19/28), with statistically significant differences (χ2=4.286, P=0.038; χ2=6.687, P=0.010). The median OS of intercalated combination of osimertinib and docetaxel group was 10.0 months, which was longer than that of osimertinib group (9.0 months), with statistically significant difference (χ2=5.917, P=0.015). Moreover, the adverse reactions in both groups were all grade Ⅰ or Ⅱ, which could be relieved or improved through symptomatic treatment. ConclusionIntercalated treatment of osimertinib with docetaxel is safe and effective in T790M mutationpositive lung adenocarcinoma patients with bone metastasis in the southern Hainan Province. It can prolong the survival time of patients.

Key words:Lung neoplasms,Osimertinib,Docetaxel,Bone metastasis,Southern Hainan Province

Chen Long, Lin Ling, Wang Cuiying, Wang Lin, He Donglei, Feng Jun. Clinical research of intercalated combination of osimertinib and docetaxel in T790M mutationpositive lung adenocarcinoma patients with bone metastasis in the southern Hainan Province[J]. Journal of International Oncology, 2019, 46(7): 399-403.

References

［1］ Cetin K, Christiansen CF, Jacobsen JB, et al. Bone metastasis, skeletalrelated events, and mortality in lung cancer patients: a Danish populationbased cohort study［J］. Lung Cancer, 2014, 86(2): 247254. DOI: 10.1016/j.lungcan.2014.08.022. ［2］ Reck M, Popat S, Reinmuth N, et al. Metastasis non small cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow up［J］. Ann Oncol, 2014, 25 Suppl 3: iii27iii39. DOI: 10.1093/annonc/mdu199. ［3］ Yashima H, Shimizu K, Araki T, et al. Assessment of DDR2, BRAF, EGFR and KRAS mutations as therapeutic targets in nonadenocarcinoma lung cancer patients［J］. Mol Clin Oncol, 2014, 2(5): 714718. DOI: 10.3892/mco.2014.302. ［4］中国临床肿瘤学会指南工作委员会. 中国临床肿瘤学会原发性肺癌诊疗指南（2018年版）［M］. 人民卫生出版社, 2018: 4950. ［5］ Su KY, Chen HY, Li KC, et al. Pretreatment epidermal growth factor receptor (EGFR) T790M mutation predicts shorter EGFR tyrosine kinase inhibitor response duration in patients with nonsmall cell lung cancer［J］. J Clin Oncol, 2012, 30(4): 433440. DOI: 10.1200/JCO.2011.38.3224. ［6］刘曦光. 化疗与埃克替尼间插治疗在EGFR突变型非小细胞肺癌术后辅助治疗中的疗效与安全性［D］. 广州: 南方医科大学, 2016. ［7］王洁, 皮灿. 奥希替尼与培美曲塞联合铂类化疗在EGFRT790M阳性非小细胞肺癌患者中的疗效比较［J］. 循证医学, 2018, 18(1): 3639. ［8］ Wu YL, Lee JS, Thongprasert S, et al. Intercalated combination of chemotherapy and erlotinib for patients with advanced stage nonsmallcell lung cancer (FASTACT2): a randomized, double blind trial［J］. Lancet Oncl, 2013, 14(8): 777786. DOI: 10.1016/S14702045(13)702547. ［9］ Cheng Y, Murakami H, Yang PC, et al. Randomized phase Ⅱ trial of gefitinib with and without pemetrexed as firstline therapy in patients with advanced nonsquamous nonsmallcell lung cancer with activating epidermal growth factor receptor mutations［J］. J Clin Oncol, 2016, 34(27): 32583266. DOI: 10.1200/JCO.2016.66.9218. ［10］钱琳. 晚期非小细胞肺癌患者进行单药多西他赛二线治疗的临床研究［J］. 临床医药文献杂志, 2018, 15(5): 105106. ［11］ Jnne PA, Yang JC, Kim DW, et al. AZD9291 in EGFR inhibitorresistant nonsmallcell lung cancer［J］. N Engl J Med, 2015, 372(18): 16891699. DOI: 10.1056/NEJMoa1411817. ［12］ Zhou T, Zeng SX, Ye DW, et al. A multicenter, randomized clinical trial comparing the threeweekly docetaxel regimen plus prednisone versus mitoxantone plus prednisone for Chinese patients with metastatic castration refractory prostate cancer［J］. PLoS One, 2015, 7: e0117002. DOI: 10.1371/journal.pone.0117002. ［13］胡林军，李长岭，寿建忠，等. 多西他赛治疗转移性去势抵抗性前列腺癌的耐受剂量及其与预后的关系［J］. 中华泌尿外科杂志, 2019, 40(1): 3136. DOI: 10.3760/cma.j.issn.10006702.2019.01.006.

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