PD-1/PD-L1和CTLA-4免疫检查点抑制剂在小细胞肺癌中的临床研究进展

Advance on PD⁃1/PD⁃L1 and CTLA⁃4 immune checkpoint inhibitors in small cell lung cancer

小细胞肺癌(SCLC)属于高度恶性神经内分泌癌,早期即易发生转移,确诊时60%~70%已处于广泛期,手术治疗机会小。虽然SCLC起始对含铂方案系统化疗±放疗的一线治疗高度敏感,但多数在一线治疗后短期内即出现复发与转移。尽管近30年来对SCLC治疗不断探索与研究,仍缺乏有效治疗手段,患者长期生存率极低。近年来以免疫检查点抑制剂(ICIs)为代表的肿瘤免疫治疗在SCLC中初露锋芒,多项临床试验显示以程序性死亡受体-1及其配体(PD-1/PD-L1)和细胞毒性T淋巴细胞相关抗原-4(CTLA-4)为靶点的ICIs具有持久疗效,为SCLC患者带来了长期生存的希望。本文主要对PD-1/PD-L1及CTLA-4抑制剂在SCLC的临床疗效及其疗效预测生物标志物的现有证据及正在进行的临床研究进行综述。

Small cell lung cancer(SCLC)is a kind of highly malignant neuroendocrine tumor,with early development of widespread metastases.At the time of diagnosis,60%to 70%of the patients are already at extensive stage,and the chance of surgical treatment is small.Although shows excellent initial response to platinum⁃based systemic chemotherapy±radiotherapy,most patients with SCLC suffer rapid disease relapse within a short period of time after the first⁃line treatment.Despite decades of effort on the treatment of SCLC,a paucity of effective treatment exists for recurrent disease,and the long⁃term survival rate is very low,which has not been effectively improved.In recent years,immunotherapy represented by immune checkpoint inhibitors(ICIs),has emerged in the treatment of SCLC.A number of clinical trials have shown that ICIs targeting programmed death receptor⁃1/ligand⁃1(PD⁃1/PD⁃L1)and cytotoxic T lymphocyte associated antigen⁃4(CTLA⁃4)has lasting efficacy and activity,which brings hope for long⁃term survival of patients with SCLC.This review mainly describes the available data on clinical efficacy of PD⁃1/PD⁃L1 and CTLA⁃4 inhibitors,the emerging evidence regarding biomarkers,as well as ongoing clinical trials,and discusses the challenges and application prospects of ICIs in SCLC.