Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea.
Center for Precision Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Ann Lab Med. 2023 Jan 1;43(1):64-72. doi: 10.3343/alm.2023.43.1.64. Epub 2022 Sep 1.
Following success of the phase III PROfound trial, the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib was approved by the US Food and Drug Administration in May 2020 for adult patients with deleterious homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC). As locally adopted multigene panel next-generation sequencing (NGS) assays for selecting PARP inhibitor candidates have not been thoroughly evaluated, we compared the analytical performance of the FoundationOne CDx (Foundation Medicine, Inc., Cambridge, MA, USA) (central laboratory) and other NGS assays (local laboratory) with samples from the PROfound trial in Korea.
One hundred PROfound samples (60 HRR mutation [HRRm] cases and 40 non-HRRm cases) were analyzed. The results of HRR gene mutation analysis were compared between the FoundationOne CDx and two other NGS assays [SureSelect Custom Design assay (Agilent Technologies, Inc., Santa Clara, CA, USA) and Oncomine Comprehensive assay (Thermo Fisher Scientific, Inc., Waltham, MA, USA)].
The positive percent agreement for single nucleotide variants (SNVs) and insertion/deletions (indels) between the central laboratory and local laboratory was 98.7%-100.0%. The negative percent agreement and overall percent agreement (OPA) for SNVs and indels between central and local laboratories were both 100%. Compared with that of the FoundationOne CDx assay, the OPA for copy number variations of the Oncomine Comprehensive and SureSelect Custom assays reached 99.8%-100%. Most mCRPC patients harboring a deleterious genetic variant were successfully identified with both local laboratory assays.
The NGS approach at a local laboratory showed comparable analytical performance for identifying HRRm status to the FoundationOne CDx assay used at the central laboratory.
在 III 期 PROfound 试验取得成功后，聚 ADP-核糖聚合酶（PARP）抑制剂奥拉帕利于 2020 年 5 月获得美国食品和药物管理局批准，用于治疗有害同源重组修复（HRR）基因突变的转移性去势抵抗性前列腺癌（mCRPC）成年患者。由于用于选择 PARP 抑制剂候选药物的本地采用的多基因面板下一代测序（NGS）检测尚未得到充分评估，我们比较了韩国 PROfound 试验中的样本中 FoundationOne CDx（Foundation Medicine，Inc.，马萨诸塞州剑桥市，美国）（中心实验室）和其他 NGS 检测（本地实验室）的分析性能。
分析了 100 个 PROfound 样本（60 个 HRR 基因突变 [HRRm]病例和 40 个非 HRRm 病例）。比较了 FoundationOne CDx 与另外两种 NGS 检测（SureSelect Custom Design 检测（Agilent Technologies，Inc.，加利福尼亚州圣克拉拉市）和 Oncomine Comprehensive 检测（Thermo Fisher Scientific，Inc.，马萨诸塞州沃尔瑟姆市））的 HRR 基因突变分析结果。
中心实验室和本地实验室之间单核苷酸变异（SNV）和插入/缺失（indel）的阳性百分比一致率为 98.7%-100.0%。SNV 和 indel 的阴性百分比一致率和总百分比一致率（OPA）在中心和本地实验室均为 100%。与 FoundationOne CDx 检测相比，Oncomine Comprehensive 和 SureSelect Custom 检测的拷贝数变异的 OPA 达到 99.8%-100%。两种本地实验室检测均成功识别出大多数携带有害遗传变异的 mCRPC 患者。
本地实验室的 NGS 方法在鉴定 HRRm 状态方面与中心实验室使用的 FoundationOne CDx 检测具有相当的分析性能。
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