introduction：durvalumab is a selective, high-affinity human igg1 monoclonal antibody that blocks programmed cell death ligand-1 (pd-l1) binding to pd-1. here we report safety and clinical activity in the non-small cell lung cancer (nsclc) cohort of a phase 1/2 trial that included multiple tumor types (study 1108; nct01693562).
methods：patients with stage iiib-iv nsclc (squamous or nonsquamous) received durvalumab 10 mg/kg q2w for 12 months or until confirmed progressive disease or unacceptable toxicity. primary objectives were safety and antitumor activity. tumoral pd-l1 expression was assessed using the ventana sp263 assay. responses were assessed by blinded independent central review (recist v1.1). adverse events were graded according to nci ctcae v4.03.
方法：iiib-iv期nsclc(鳞状或非鳞状)患者接受durvalumab 10 mg/kg q2w连续治疗12个月，或直至确诊为疾病进展或出现不可接受的毒性。主要研究结果为安全性和抗肿瘤活性。采用ventana sp263法检测肿瘤pd-l1的表达。由盲法独立中央评审根据recist v1.1评估治疗反应。不良事件按nci ctcae v4.03进行分级。
results：of 304 patients, 79.0% were previously treated. confirmed objective response rate was 21.8% in patients with ≥25% pd-l1 expression and 6.4% in those with <25%; 25.9% in first-line patients and 12.7% in previously treated patients; 14.0% in squamous and 16.7% in nonsquamous disease. median os was 12.4 months and median pfs was 1.7 months; both were numerically longer in the pd-l1 ≥25% group than in the pd-l1 <25% group (os 16.4 vs 7.6 months; pfs 2.6 vs 1.4 months). treatment-related adverse events occurred in 57.2%, were grade 3/4 in 10.2%, and led to discontinuation in 5.6%. one patient (0.3%) died of treatment-related pneumonia with underlying pneumonitis.
结果：304例患者中，79.0%曾接受过治疗。经证实，pd-l1表达≥25%的患者客观缓解率为21.8%，pd-l1表达<25%的患者客观缓解率为6.4%；一线治疗患者客观缓解率为25.9%，既往治疗患者为12.7%；鳞状细胞癌患者客观缓解率为14.0%，非鳞状细胞癌为16.7%。中位os为12.4个月，中位pfs为1.7个月；在生存时间上，pd-l1 ≥25%组高于pd-l1 <25%组(os 16.4 vs 7.6个月；pfs 2.6 vs . 1.4个月)。与治疗相关的不良事件发生率为57.2%，其中3/4级为10.2%，5.6%因不良反应导致终止治疗。1例患者(0.3%)因并发潜在肺炎，死于治疗相关的肺炎。
conclusions：durvalumab was clinically active irrespective of histology in this mostly pretreated population, with a manageable safety profile. response rates and survival appeared to be enhanced in patients with greater tumoral pd-l1 expression.