First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer
First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer
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DOI：
10.1056/nejmoa1809064
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发表时间：
2018-12-06
影响因子：
158.5
通讯作者：
Liu, S. V.
中科院分区：
文献类型：
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作者：
Horn, L.;Mansfield, A. S.;Liu, S. V.
通过抑制程序性死亡配体1（PD-L1）-程序性死亡1（PD-1）信号传导来增强肿瘤特异性T细胞免疫，已显示出治疗广泛期小细胞肺癌的前景。结合检查点抑制与细胞毒化疗可能有协同作用，提高efficacy. METHODS我们进行了这一双盲，安慰剂对照，3期试验，以评估atezolizumab加卡铂和依托泊苷广泛期小细胞肺癌患者谁以前没有接受过治疗。患者以1：1的比例随机分配接受卡铂和依托泊苷联合atezolizumab或安慰剂治疗4个21天周期（诱导期），随后是维持期，在此期间接受atezolizumab或安慰剂（根据先前的随机分配），直至出现不可接受的毒性反应、根据实体瘤疗效评价标准（1.1版）的疾病进展或无额外的临床获益。两个主要终点是意向治疗人群中经评估的无进展生存期和总生存期，共有201例患者随机分配至atezolizumab组，202例患者随机分配至安慰剂组。在中位随访13.9个月时，atezolizumab组的中位总生存期为12.3个月，安慰剂组为10.3个月（死亡风险比为0.70; 95%置信区间[CI]为0.54 - 0.91; P = 0.007）。中位无进展生存期分别为5.2个月和4.3个月（疾病进展或死亡的风险比为0.77; 95%CI为0.62 - 0.96; P = 0.02）。atezolizumab加卡铂和依托泊苷的安全性与先前报道的安全性个人代理，没有新的调查结果observed.CONCLUSIONSThe除了atezolizumab化疗的一线治疗广泛期小细胞肺癌导致显着更长的总生存期和无进展生存期比单独化疗。
BACKGROUNDEnhancing tumor-specific T-cell immunity by inhibiting programmed death ligand 1 (PD-L1)-programmed death 1 (PD-1) signaling has shown promise in the treatment of extensive-stage small-cell lung cancer. Combining checkpoint inhibition with cytotoxic chemotherapy may have a synergistic effect and improve efficacy.METHODSWe conducted this double-blind, placebo-controlled, phase 3 trial to evaluate atezolizumab plus carboplatin and etoposide in patients with extensive-stage small-cell lung cancer who had not previously received treatment. Patients were randomly assigned in a 1:1 ratio to receive carboplatin and etoposide with either atezolizumab or placebo for four 21-day cycles (induction phase), followed by a maintenance phase during which they received either atezolizumab or placebo (according to the previous random assignment) until they had unacceptable toxic effects, disease progression according to Response Evaluation Criteria in Solid Tumors, version 1.1, or no additional clinical benefit. The two primary end points were investigator-assessed progression-free survival and overall survival in the intention-to-treat population.RESULTSA total of 201 patients were randomly assigned to the atezolizumab group, and 202 patients to the placebo group. At a median follow-up of 13.9 months, the median overall survival was 12.3 months in the atezolizumab group and 10.3 months in the placebo group (hazard ratio for death, 0.70; 95% confidence interval [CI], 0.54 to 0.91; P = 0.007). The median progression-free survival was 5.2 months and 4.3 months, respectively (hazard ratio for disease progression or death, 0.77; 95% CI, 0.62 to 0.96; P = 0.02). The safety profile of atezolizumab plus carboplatin and etoposide was consistent with the previously reported safety profile of the individual agents, with no new findings observed.CONCLUSIONSThe addition of atezolizumab to chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer resulted in significantly longer overall survival and progression-free survival than chemotherapy alone.