Phase 2 Study of Talazoparib in Patients With Homologous Recombination Repair-Deficient Squamous Cell Lung Cancer: Lung-MAP Substudy S1400G.
Phase 2 Study of Talazoparib in Patients With Homologous Recombination Repair-Deficient Squamous Cell Lung Cancer: Lung-MAP Substudy S1400G.
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DOI：
10.1016/j.cllc.2021.01.001
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发表时间：
2021-05
影响因子：
3.6
通讯作者：
Gandara DR
中科院分区：
文献类型：
--
作者：
Owonikoko TK;Redman MW;Byers LA;Hirsch FR;Mack PC;Schwartz LH;Bradley JD;Stinchcombe TE;Leighl NB;Al Baghdadi T;Lara P Jr;Miao J;Kelly K;Ramalingam SS;Herbst RS;Papadimitrakopoulou V;Gandara DR
本信号发现研究旨在评估talazoparib治疗晚期肺癌鳞状细胞同源重组修复缺陷（Homologous Recombination Repair Deficiency， HRRD）的疗效。完全符合条件的人群（FEP）在任何研究定义的HRR基因中都有有害突变的肿瘤，并且之前没有暴露于PARP抑制剂。主要分析人群（PAP）是具有ATM、ATR、BRCA1、BRCA2或PALB2基因改变的FEP的一个子集。治疗包括talazoparib每日1mg，连续21天为一个周期。两阶段设计具有精确的93%功率和单侧0.07水平的I型误差，需要入组40例PAP患者，以便在真实ORR≥35%时排除ORR为15%或更低的情况。该研究纳入了47例FEP患者，其中24例PAP患者。FEP的中位年龄为66.7岁；男性：83%和85%是白人。PAP的总缓解率（ORR）为4% (95%CI: 0,21)，疾病控制率（DCR）为54% (95%CI: 33,74)；中位PFS和OS分别为2.4个月（95%CI: 1.5-2.8）和5.2个月（95%CI: 4.0-10）。在FEP中，ORR为11% (95%CI: 3.6, 23)；DCR为51% (95%CI: 36, 66)，中位缓解持续时间为1.8个月（95%CI: 1.3, 4.2）；中位PFS和OS分别为2.5个月和5.7个月。S1400G在伴有HRRD的鳞状肺癌的生物标志物定义亚群中，单药talazoparib未能显示出足够的疗效。
This signal finding study was designed to evaluate the efficacy of talazoparib in advanced stage squamous cell lung cancer harboring Homologous Recombination Repair Deficiency (HRRD). The full eligible population (FEP) had tumors with a deleterious mutation in any of the study-defined HRR genes and without prior exposure to a PARP inhibitor. The primary analysis population (PAP) is a subset of FEP with alteration in ATM, ATR, BRCA1, BRCA2, or PALB2]. Treatment consisted of talazoparib 1mg daily, continuously in 21-day cycles. A 2-stage design with exact 93% power and 1-sided 0.07 level type I error required enrollment of 40 patients in the PAP in order to rule out an ORR of 15% or less if the true ORR is ≥35%. The study enrolled 47 patients in the FEP of whom 24 were in the PAP. The median age for the FEP was 66.7 years; male: 83% and 85% White. Overall response rate (ORR) in the PAP was 4% (95%CI: 0, 21) with disease control rate (DCR) of 54% (95%CI: 33, 74); median PFS and OS of 2.4 months (95%CI: 1.5-2.8) and 5.2 months (95%CI: 4.0-10), respectively. In the FEP, ORR was 11% (95%CI: 3.6, 23); DCR of 51% (95%CI: 36, 66) and median duration of response was 1.8 months (95% CI: 1.3, 4.2); median PFS and OS were 2.5 months and 5.7 months, respectively. S1400G failed to show sufficient level of efficacy for single agent talazoparib in a biomarker defined subset of squamous lung cancer with HRRD.
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影响因子：
51.1
作者：
Pujade-Lauraine, Eric;Ledermann, Jonathan A.;Pautier, Patricia
通讯作者：
Pautier, Patricia
影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
DOI：
10.1158/1078-0432.ccr-13-3473
发表时间：
2015-04-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Herbst RS;Gandara DR;Hirsch FR;Redman MW;LeBlanc M;Mack PC;Schwartz LH;Vokes E;Ramalingam SS;Bradley JD;Sparks D;Zhou Y;Miwa C;Miller VA;Yelensky R;Li Y;Allen JD;Sigal EV;Wholley D;Sigman CC;Blumenthal GM;Malik S;Kelloff GJ;Abrams JS;Blanke CD;Papadimitrakopoulou VA
通讯作者：
Papadimitrakopoulou VA
影响因子：
11.2
作者：
McCabe, Nuala;Turner, Nicholas C.;Ashworth, Alan
通讯作者：
Ashworth, Alan
影响因子：
5.7
作者：
Murai J;Huang SY;Renaud A;Zhang Y;Ji J;Takeda S;Morris J;Teicher B;Doroshow JH;Pommier Y
通讯作者：
Pommier Y