靶向程序性死亡分子1抑制剂治疗晚期鳞状非小细胞肺癌2例并文献复习

Treatment of advanced squamous non-small cell lung cancer with programmed cell death ligand 1 inhibitors: a report of two cases and literature review

目的靶向程序性死亡分子1(programmed cell death ligand 1,PD-1)通路的肿瘤免疫治疗在多种类型肿瘤中取得了卓越的临床疗效,包括非小细胞肺癌(non-small cell lung carcinoma,NSCLC)。本研究关注2种靶向结合PD-1受体的单克隆抗体Pembrolizumab和Nivolumab一线治疗在我国晚期NSCLC患者中的疗效。方法 2例未接受过任何治疗的确诊为晚期鳞状NSCLC患者,患者甲给予Pembrolizumab 100mg/3w、患者乙给予Nivolumab 2 mg/(kg·2 w),均静脉注射,定期评估疗效。结果经2周期治疗后,2例患者肺部肿瘤均达部分缓解(partial response,PR),呼吸系统症状及炎症好转;患者甲最终因肺癌脑转移于免疫治疗第3周期后死亡。患者乙治疗期间肺部原发病灶逐渐缩小,疗效评价PR;拟行第4周期治疗时发现脑部多发转移瘤,拟行第5周期时脑部多发转移瘤较前略有增大,疗效评价稳定(stable disease,SD),迄今仍在维持治疗。治疗期间,2例患者肿瘤标志物CA125均显著下降。治疗期间未观察到不良反应。结论初步研究显示PD-1抑制剂治疗晚期NSCLC原发病灶疗效显著,安全性好,血清CA125浓度可作为一个评价疗效的观察指标。但PD-1抑制剂对控制脑部转移灶的疗效需要进一步研究。由于本研究入组人数较少,此结论尚需得到进一步的论证。

Objective Tumor immunotherapy targeting programmed cell death ligand 1(PD-1)receptor signal pathway has achieved a remarkableclinical outcomes on multiple types of tumors including non-small cell lung cancer(NSCLC).The study was to evaluate firstline therapy of two main PD1 inhibitors,pembrolizumab and nivolumab,with regard to activity and feasibility in advanced NSCLC in China.Methods Two patients with advanced squamous NSCLC who had not received treatment previously were treated with intravenous pembrolizumab(100 mg every 3 weeks),or nivolumab(2 mg/kg every 2 weeks),respectively.Tumor response was assessed by RECIST v1.1 every one or two periods.Results After treatment for 2 periods,both patients experienced partial response(PR)of lung cancer,and respiratory symptoms improved significantly and inflammation relieved.But unfortunately the patient treated with pembrolizum was observed brain metastates and finally died of the progressive brain metastases when assigning the 3 rd treatment.The other patient treated with nivolumab was observed stable and obvious improvement of lung caner with PR,but multiple brain metastases when assigned the 4 th therapy which increased slightly when assigned the 5 th treatment with stable disease(SD).During the immunotherapy,the blood concentration of CA125 decreased significantly and no adverse reactions were observed in both patients.Conclusion Preliminary studies have shown significant efficacy and safety by treatment with PD-1 inhibitors in advanced primary NSCLC,and blood concentration of CA125 may be considered as an index of outcome.However,PD-1 inhibitors could not relieve the progression of brain metastases.And this conclusion needs to be verified by enrolling more patients and further study.