奥希替尼间歇插入多西他赛治疗海南南部肺腺癌并骨转移T790M基因突变阳性患者的临床研究

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

目的探讨奥希替尼间歇插入多西他赛治疗海南南部肺腺癌并骨转移T790M基因突变阳性患者的临床应用.方法入组2018年1月-2018年10月海南省第三人民医院收治的海南南部肺腺癌并骨转移T790M基因突变阳性患者,根据治疗用药分为奥希替尼间歇插入化疗组(n=32)和奥希替尼组(n=28).奥希替尼间歇插入化疗组患者口服奥希替尼80mg1次/d,待病情进展插入静脉滴注多西他赛75mg/m^2化疗,1次/3周,待肿瘤治疗评价稳定或缓解,则口服奥希替尼80mg1次/d维持直至进展后再行多西他赛化疗.奥希替尼组患者口服奥希替尼80mg1次/d.两组患者均联合应用唑来膦酸.比较两组患者的有效率、疾病控制率、总生存期及不良反应发生率.结果奥希替尼间歇插入化疗组患者的有效率为62.5%(20/32),高于奥希替尼组的35.7%(10/28),两组差异有统计学意义(χ^2=4.286,P=0.038);奥希替尼间歇插入化疗组患者的疾病控制率为93.8%(30/32),高于奥希替尼组的67.9%(19/28),两组差异有统计学意义(χ^2=6.687,P=0.010).奥希替尼间歇插入化疗组患者的中位总生存期为10.0个月,较奥希替尼组的9.0个月有所延长,两组差异有统计学意义(χ^2=5.917,P=0.015).两组患者不良反应均为Ⅰ或Ⅱ级,给予对症治疗后得到缓解和改善.结论奥希替尼间歇插入多西他赛化疗治疗海南南部肺腺癌并骨转移T790M基因突变阳性患者安全有效,能够延长患者生存期.

Objective To 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. Methods T790M 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/m^2, 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. Results The 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 (χ^2=4.286, P=0.038;χ^2=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 (χ^2=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. Conclusion Intercalated 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.