FIR: Efficacy, Safety, and Biomarker Analysis of a Phase II Open-Label Study of Atezolizumab in PD-L1-Selected Patients With NSCLC.
FIR: Efficacy, Safety, and Biomarker Analysis of a Phase II Open-Label Study of Atezolizumab in PD-L1-Selected Patients With NSCLC.
复制标题
DOI：
10.1016/j.jtho.2018.05.004
复制
发表时间：
2018-11
期刊：
影响因子：
--
通讯作者：
Rizvi NA
中科院分区：
文献类型：
--
作者：
Spigel DR;Chaft JE;Gettinger S;Chao BH;Dirix L;Schmid P;Chow LQM;Hicks RJ;Leon L;Fredrickson J;Kowanetz M;Sandler A;Funke R;Rizvi NA
FIR II期研究(NCT01846416)评价了抗程序性死亡配体1(PD-L1)阿替唑单抗治疗根据肿瘤细胞(TC)或肿瘤浸润性免疫细胞(IC)PD-L1表达选择的晚期非小细胞肺癌(NSCLC)的疗效和安全性。有PD-L1TC2/3(PD-L1染色在5%的TC的≥上)或IC2/3肿瘤(PD-L1染色在IC的5%的≥上；通过SP142PD-L1免疫组织化学方法确定)的患者被纳入队列1(化疗-单纯/GT；辅助化疗和复发之间的6个月)、队列2(≥二线无脑转移)或队列3(≥二线治疗脑转移)。患者接受1200 mg阿替唑单抗治疗，第1天(21天为一个周期)。主要终点：研究人员评估的实体肿瘤改良反应评估标准(MRECIST)，客观反应率(ORR；RECIST v1.1)。次要终点：总存活率、无进展存活率、反应持续时间、安全性。纳入138例患者(137例可评价疗效：队列1，n=31；队列2，n=93；队列3，n=13)。研究人员评估的ORR在队列1、2和3分别为32%、21%和23%。81%、67%和69%的患者报告了与治疗相关的不良事件(TRAE)，其中3-4级TRAE的发生率分别为16%、19%和15%。此外，88.6%(n=86/97)的配对基线肿瘤样本中TC/IC PD-L1的表达随时间发生了5%的变化。阿替唑单抗治疗在非小细胞肺癌患者中显示出临床活性，包括脑转移患者；安全性与先前的试验一致。阿替唑珠单抗已经完成了二线的III期单一疗法研究；一线试验正在进行中，证实了这些有利的结果。
The FIR phase II study (NCT01846416) evaluated the efficacy and safety of anti-programmed death-ligand 1 (PD-L1) atezolizumab in advanced non-small-cell lung cancer (NSCLC) selected by tumor cell (TC) or tumor-infiltrating immune cell (IC) PD-L1 expression. Patients with PD-L1 TC2/3 (PD-L1 staining on ≥5% of TC) or IC2/3 tumors (PD-L1 staining on ≥5% of IC; determined by SP142 PD-L1 immunohistochemistry assay) with paired fresh and archival histology samples were recruited into Cohort 1 (chemotherapy-naïve/>6 months between adjuvant chemotherapy and recurrence), Cohort 2 (≥ second-line without brain metastases), or Cohort 3 (≥ second-line with treated brain metastases). Patients received 1200 mg atezolizumab, Day 1 (21-day cycles). Primary endpoint: investigator-assessed modified Response Evaluation Criteria in Solid Tumors (mRECIST), objective response rate (ORR; RECIST v1.1). Secondary endpoints: overall survival, progression-free survival, duration of response, safety. Patients (n=138) were enrolled (137 evaluable for response: Cohort 1, n=31; Cohort 2, n=93; Cohort 3, n=13). Investigator-assessed ORR was 32%, 21%, and 23% for Cohorts 1, 2, and 3, respectively. Treatment-related adverse events (TRAEs) were reported in 81%, 67%, and 69% of patients, respectively, including grade 3–4 TRAEs in 16%, 19%, and 15%. Moreover, 88.6% (n=86/97) paired baseline tumor samples had <5% change in TC/IC PD-L1 expression over time. Atezolizumab monotherapy showed clinical activity in patients with NSCLC, including those with brain metastases; safety was consistent with previous trials. Atezolizumab has completed phase III monotherapy studies in second-line; front-line trials are ongoing, confirming these favorable results.
登录
查看更多内容
影响因子：
50.5
作者：
Ilie, M.;Long-Mira, E.;Hofman, P.
通讯作者：
Hofman, P.
影响因子：
64.8
作者：
Herbst RS;Soria JC;Kowanetz M;Fine GD;Hamid O;Gordon MS;Sosman JA;McDermott DF;Powderly JD;Gettinger SN;Kohrt HE;Horn L;Lawrence DP;Rost S;Leabman M;Xiao Y;Mokatrin A;Koeppen H;Hegde PS;Mellman I;Chen DS;Hodi FS
通讯作者：
Hodi FS
DOI：
10.1016/s0140-6736(16)32517-x
发表时间：
2017-01-21
期刊：
Lancet (London, England)
影响因子：
--
作者：
Rittmeyer A;Barlesi F;Waterkamp D;Park K;Ciardiello F;von Pawel J;Gadgeel SM;Hida T;Kowalski DM;Dols MC;Cortinovis DL;Leach J;Polikoff J;Barrios C;Kabbinavar F;Frontera OA;De Marinis F;Turna H;Lee JS;Ballinger M;Kowanetz M;He P;Chen DS;Sandler A;Gandara DR;OAK Study Group
通讯作者：
OAK Study Group
影响因子：
45.3
作者：
Shepherd, FA;Dancey, J;Berille, J
通讯作者：
Berille, J
影响因子：
168.9
作者：
Fehrenbacher, Louis;Spira, Alexander;Rittmeyer, Achim
通讯作者：
Rittmeyer, Achim