Genetics Department, Institut Curie and Paris Sciences Lettres University, Paris, France.
Laboratoire de Biologie Clinique et Oncologique, Centre François Baclesse, Caen, France.
J Natl Cancer Inst. 2021 Jul 1;113(7):917-923. doi: 10.1093/jnci/djaa193.
PAOLA1 is a phase III study assessing olaparib maintenance therapy in advanced high-grade ovarian carcinoma patients responding to first-line platinum-taxane-based chemotherapy plus bevacizumab as standard of care. Randomization was stratified by treatment outcome and tumor BRCA1/2 status (tBRCA) at screening.
tBRCA was tested on formalin-fixed, paraffin-embedded tumor blocks on 5 French platforms using 2 next-generation sequencing methods based either on hybrid capture or amplicon technology. One of the exploratory objectives was to assess the concordance between germline (gBRCA) and tBRCA testing in French patients. gBRCA testing was performed on blood samples on the same platforms.
From May 2015 to July 2017, tBRCA tests were performed for 1176 screened patients. Only 52 (4.4%) tumor samples were noncontributive. The median interval between reception of the tumor sample and availability of the tBRCA status result was 37 days (range = 8-260). A pathogenic variant was reported in 27.1% tumor samples (319 of 1176 screened patients). tBRCA and gBRCA testing were performed for 451 French patients with negative results for both tests in 306 patients (67.8%) and positive results for both tests in 85 patients (18.8%). Only 1 large genomic rearrangement of BRCA1 was detected, exclusively in the blood sample. Interestingly, tBRCA testing revealed 6.4% of pathogenic variant (29 of 451) not detected by gBRCA testing.
tBRCA testing is an appropriate tool with an acceptable turnaround time for clinical practice and a low failure rate, ensuring reliable identification of patients likely to benefit from poly(ADP-ribose) polymerase inhibitor therapy.
PAOLA1 是一项评估奥拉帕利维持治疗在对一线含铂紫杉醇化疗加贝伐珠单抗标准治疗有反应的晚期高级别卵巢癌患者中的疗效的 III 期研究。随机分组按治疗结果和筛选时的肿瘤 BRCA1/2 状态（tBRCA）分层。
使用基于杂交捕获或扩增子技术的 2 种下一代测序方法，在 5 个法国平台上对福尔马林固定、石蜡包埋的肿瘤块进行 tBRCA 检测。其中一个探索性目标是评估法国患者中胚系（gBRCA）和 tBRCA 检测的一致性。gBRCA 检测在同一平台上的血液样本上进行。
从 2015 年 5 月至 2017 年 7 月，对 1176 名筛选患者进行了 tBRCA 检测。只有 52 个（4.4%）肿瘤样本无贡献。从收到肿瘤样本到获得 tBRCA 状态结果的中位时间间隔为 37 天（范围为 8-260 天）。在 1176 名筛选患者中，有 27.1%（319 名）的肿瘤样本报告存在致病性变异。对 451 名法国患者进行了 tBRCA 和 gBRCA 检测，在 306 名患者中，两种检测均为阴性，在 85 名患者中，两种检测均为阳性。仅在 1 名患者的血液样本中检测到 BRCA1 的 1 个大基因组重排。有趣的是，tBRCA 检测发现了 gBRCA 检测未检测到的致病性变异 6.4%（29 名患者）。
tBRCA 检测是一种合适的工具，具有可接受的周转时间和较低的失败率，可确保可靠地识别可能受益于聚（ADP-核糖）聚合酶抑制剂治疗的患者。
