奥拉帕尼联合帕博利珠单抗二线治疗广泛期小细胞肺癌的疗效和安全性

Efficacy of olaparib combined with pembrolizumab in second-line treatment for extensive-stage small cell lung cancer

目的:分析40~80岁广泛期小细胞肺癌(SCLC)患者接受二线奥拉帕尼联合帕博利珠单抗治疗以及帕博利珠单抗单药治疗的疗效和安全性。方法:选取2017年3月至2019年10月就诊于解放军总医院的一线标准化疗方案后进展或复发的SCLC患者21例,联合组接受奥拉帕尼(300 mg口服,每日2次)联合帕博利珠单抗(200 mg静脉滴注,每3周1次)治疗;单药组接受帕博利珠单抗(200 mg静脉滴注,每3周1次)治疗。结果:联合组和单药组患者的客观有效率分别为45.5%和10.0%(P=0.149),疾病控制率分别为81.8%和70.0%(P=0.635),中位无进展生存时间分别为5.93和3.53个月(P=0.036),中位总生存时间分别为10.43和8.43个月(P=0.063)。联合组和单药组患者的不良反应发生率分别为90.9%和70.0%(P=0.311),Ⅲ级及以上不良反应包括骨髓抑制(36.4%和10.0%,P=0.311)、胃肠道反应(9.1%和10.0%,P=1.000)和其他免疫相关不良反应(18.2%和30.0%,P=1.000)。多因素分析显示,转移灶数目(P=0.006)、铂类敏感性(P=0.036)和乳酸脱氢酶水平(P=0.022)为影响患者联合用药疗效的独立因素。结论:帕博利珠单抗联合奥拉帕尼初步显示较好的疗效,安全性可耐受,或可成为SCLC患者二线治疗方案的选择。

Objective To compare the efficacy and safety of olaparib in combination with pembrolizumab with pembrolizumab alone in second-line treatment for patients with extensive stage-small cell lung cancer(ES-SCLC)whose ages ranged from 40 to 80 years.Methods From March 2017 to October 2019,21 patients with progressed or relapsed small cell lung cancer after standard first line treatment were enrolled in this study.The olaparib/pembrolizumab group(n=11)was treated by olaparib 300mg twice per day combined with pembrolizumab 200mg once every 3 weeks,while pembrolizumab group was treated by pembrolizumab alone.Results The objective response rate(ORR)of olaparib/pembrolizumab group and pembrolizumab group were 45.5% and 10.0%,respectively(P=0.149),and the disease control rate(DCR)were 81.8% and 70.0%(P=0.635).The median progression-free survival(PFS)were 5.93 months and 3.53 months(P=0.036),the median overall survival(OS)were 10.43 months and 8.43 months(P=0.063).The adverse reaction incidences of all grades were 90.9% and 70.0%(P=0.311),and the incidences of grade Ⅲ-Ⅴ including myelosuppression were 36.4% and 10.0%(P=0.311),gastrointestinal reaction were 9.1% and 10.0%,(P=1.000)and other immune-related adverse events were 18.2% and 30.0%(P=1.000).Further analysis showed the metastatic number(P=0.006),platinum sensitivity(P=0.036)and LDH level(P=0.022)significantly affected the ORR of olaparib/pembrolizumab therapy.Conclusion Our preliminary study indicates that olaparib combined with pembrolizumab is an efficient and safe second-line treatment therapy for patients with ES-SCLC.