Turner Nicholas C, Laird A Douglas, Telli Melinda L, Rugo Hope S, Mailliez Audrey, Ettl Johannes, Grischke Eva-Maria, Mina Lida A, Balmaña Judith, Fasching Peter A, Hurvitz Sara A, Hopkins Julia F, Albacker Lee A, Chelliserry Jijumon, Chen Ying, Conte Umberto, Wardley Andrew M, Robson Mark E
The Royal Marsden Hospital, The Institute of Cancer Research, London, UK.
Pfizer Inc., La Jolla, CA, USA.
NPJ Breast Cancer. 2023 Oct 6;9(1):81. doi: 10.1038/s41523-023-00561-y.
These analyses explore the impact of homologous recombination repair gene mutations, including BRCA1/2 mutations and homologous recombination deficiency (HRD), on the efficacy of the poly(ADP-ribose) polymerase (PARP) inhibitor talazoparib in the open-label, two-cohort, Phase 2 ABRAZO trial in germline BRCA1/2-mutation carriers. In the evaluable intent-to-treat population (N = 60), 58 (97%) patients harbor ≥1 BRCA1/2 mutation(s) in tumor sequencing, with 95% (53/56) concordance between germline and tumor mutations, and 85% (40/47) of evaluable patients have BRCA locus loss of heterozygosity indicating HRD. The most prevalent non-BRCA tumor mutations are TP53 in patients with BRCA1 mutations and PIK3CA in patients with BRCA2 mutations. BRCA1- or BRCA2-mutated tumors show comparable clinical benefit within cohorts. While low patient numbers preclude correlations between HRD and efficacy, germline BRCA1/2 mutation detection from tumor-only sequencing shows high sensitivity and non-BRCA genetic/genomic events do not appear to influence talazoparib sensitivity in the ABRAZO trial.ClinicalTrials.gov identifier: NCT02034916.
这些分析探讨了同源重组修复基因突变，包括BRCA1/2突变和同源重组缺陷（HRD），对聚（ADP-核糖）聚合酶（PARP）抑制剂他拉唑帕尼在开放标签、双队列2期ABRAZO试验中对种系BRCA1/2突变携带者疗效的影响。在可评估的意向性治疗人群（N = 60）中，58名（97%）患者在肿瘤测序中携带≥1个BRCA1/2突变，种系和肿瘤突变之间的一致性为95%（53/56），85%（40/47）的可评估患者存在BRCA基因座杂合性缺失表明存在HRD。最常见的非BRCA肿瘤突变在BRCA1突变患者中是TP53，在BRCA2突变患者中是PIK3CA。BRCA1或BRCA2突变的肿瘤在各队列中显示出相当的临床获益。虽然患者数量较少，无法建立HRD与疗效之间的相关性，但仅从肿瘤测序检测种系BRCA1/2突变显示出高敏感性，并且在ABRAZO试验中，非BRCA基因/基因组事件似乎不影响他拉唑帕尼的敏感性。临床试验注册号：NCT02034916。
Zotero 插件
