University Hospitals Leuven, Leuven Cancer Institute (LKI), KU Leuven, and Belgium and Luxembourg Gynecologic Oncology Group (BGOG), Leuven, Belgium; KU Leuven VIB Center for Cancer Biology, Lab of Translational Genetics, Leuven, Belgium.
University Hospitals Leuven, Leuven Cancer Institute (LKI), KU Leuven, and Belgium and Luxembourg Gynecologic Oncology Group (BGOG), Leuven, Belgium.
Eur J Cancer. 2023 Jul;188:131-139. doi: 10.1016/j.ejca.2023.04.020. Epub 2023 Apr 27.
The PAOLA-1/ENGOT-ov25 trial showed improved progression-free (PFS) and overall survival (OS) in homologous recombination deficient (HRD) positive patients treated with olaparib, but not when HRD negative (HRD tested with MyChoice CDx PLUS [Myriad test]).
The academic Leuven HRD test consists of capture-based targeted sequencing of genome-wide single-nucleotide polymorphisms and coding exons of eight HR genes including BRCA1, BRCA2, and TP53. We compared the predictive value of the Leuven HRD versus Myriad HRD test for PFS and OS in the randomised PAOLA-1 trial.
468 patients had left-over DNA after Myriad testing for Leuven HRD testing. Positive/negative/overall percent agreement for the Leuven versus Myriad HRD status was 95%/86%/91%, respectively. Tumours were HRD+ in 55% and 52%, respectively. In Leuven HRD+ patients, 5years PFS (5yPFS) was 48.6% versus 20.3% (HR 0.431; 95% confidence intervals (CI) 0.312-0.595) for olaparib versus placebo, respectively (Myriad test 0.409; 95% CI 0.292-0.572). In Leuven HRD+/BRCAwt patients 5yPFS was 41.3% versus 12.6% (HR 0.497; 95% CI 0.316-0.783), and 43.6% versus 13.3% (HR 0.435; 95% CI 0.261-0.727) for the Myriad test. 5yOS was prolonged in the HRD+ subgroup with both tests 67.2% versus 54.4% (HR 0.663; 95% CI 0.442-0.995) for the Leuven test, and 68.0% versus 51.8% (HR 0.596 95% CI 0.393-0.904) for the Myriad test. HRD status was undetermined in 10.7% and 9.4% of the samples, respectively.
A robust correlation between the Leuven HRD and Myriad test was observed. For HRD+ tumours, the academic Leuven HRD showed a similar difference in PFS and OS as the Myriad test.
PAOLA-1/ENGOT-ov25 试验表明，同源重组缺陷（HRD）阳性患者使用奥拉帕利治疗可改善无进展生存期（PFS）和总生存期（OS），但 HRD 阴性患者（使用 MyChoice CDx PLUS [Myriad 检测] 进行 HRD 检测）则无此获益。
学术性鲁汶 HRD 检测采用基于捕获的靶向测序技术，对基因组范围内的单核苷酸多态性和 8 个 HR 基因（包括 BRCA1、BRCA2 和 TP53）的编码外显子进行检测。我们比较了鲁汶 HRD 检测与 Myriad HRD 检测对随机分组的 PAOLA-1 试验中 PFS 和 OS 的预测价值。
在进行 Myriad 检测以进行鲁汶 HRD 检测后，有 468 例患者有剩余 DNA。鲁汶与 Myriad HRD 状态的阳性/阴性/总符合率分别为 95%/86%/91%。肿瘤的 HRD+率分别为 55%和 52%。在鲁汶 HRD+患者中，5 年 PFS（5yPFS）为奥拉帕利组 48.6%，安慰剂组 20.3%（HR 0.431；95%置信区间[CI] 0.312-0.595）（Myriad 检测分别为 0.409；95%CI 0.292-0.572）。在鲁汶 HRD+/BRCAwt 患者中，5yPFS 为奥拉帕利组 41.3%，安慰剂组 12.6%（HR 0.497；95%CI 0.316-0.783），Myriad 检测组分别为 43.6%和 13.3%（HR 0.435；95%CI 0.261-0.727）。在 HRD+亚组中，两种检测方法的 5 年 OS 均延长，鲁汶检测组为 67.2%，安慰剂组为 54.4%（HR 0.663；95%CI 0.442-0.995），Myriad 检测组为 68.0%，安慰剂组为 51.8%（HR 0.596，95%CI 0.393-0.904）。两种检测方法的样本中，HRD 状态均不确定的分别占 10.7%和 9.4%。
鲁汶 HRD 与 Myriad 检测之间存在稳健的相关性。对于 HRD+肿瘤，学术性鲁汶 HRD 在 PFS 和 OS 方面的差异与 Myriad 检测相似。
