University Clinic for Medical Oncology, Inselspital, University Hospital of Bern, University of Bern, Bern, Switzerland.
Department of Gynaecology and Gynaecologic Oncology, Bern University Hospital, University of Bern, Bern, Switzerland.
Swiss Med Wkly. 2024 Apr 15;154:3386. doi: 10.57187/s.3386.
Due to its importance for treatment and potential prevention in family members, germline testing for BRCA1/2 in patients with newly diagnosed ovarian cancer is decisive and considered a standard of care. Maintenance therapy with poly(ADP-ribose) polymerase (PARP) inhibitors substantially improves progression-free survival in patients with BRCA mutations and homologous recombination-deficient tumours by inducing synthetic lethality. In Switzerland, they are licensed only for these patients. Therefore, it is crucial to test patients early while they are receiving adjuvant chemotherapy. This study aimed to determine whether genetic counselling followed by homologous recombination deficiency testing is feasible for initialising maintenance therapy within eight weeks and cost-effective in daily practice in Switzerland compared to somatic tumour analysis of all patients at diagnosis.
This single-centre retrospective study included 44 patients with newly diagnosed high-grade serous ovarian cancer of a Federation of Gynaecology and Obstetrics (FIGO) stage of IIIA-IVB diagnosed between 12/2020 and 12/2022. It collected the outcomes of genetic counselling, germline testing, and somatic Geneva test for homologous recombination deficiency. Delays in initiating maintenance therapy, total testing costs per patient, and progression-free survival were examined to assess feasibility and cost-effectiveness in clinical practice.
Thirty-seven of 44 patients (84%) with newly diagnosed ovarian cancer received counselling, of which 34 (77%) were tested for germline BRCA and other homologous recombination repair gene mutations. Five (15%) BRCA and three (9%) other homologous recombination deficiency mutations were identified. Eleven of the remaining 26 patients (42%) had tumours with somatic homologous recombination deficiency. The mean time to the initiation of maintenance therapy of 5.2 weeks was not longer than in studies for market authorisation (SOLO1, PAOLA, and PRIMA). The mean testing costs per patient were 3880 Swiss Franks (CHF), compared to 5624 CHF if all patients were tested at diagnosis with the myChoice CDx test (p <0.0001).
Using genetic counselling to consent patients with newly diagnosed ovarian cancer for germline testing fulfils the international gold standard. Subsequent somatic homologous recombination deficiency analysis complements testing and identifies more patients who will benefit from PARP inhibitor maintenance therapy. Contrary to previous health cost model studies, the procedure does not increase testing costs in the Swiss population and does not delay maintenance therapy. Therefore, all patients should be offered a primary germline analysis. The challenge for the future will be to ensure sufficient resources for prompt genetic counselling and germline testing.
由于胚系 BRCA1/2 检测对于新诊断卵巢癌患者的治疗和潜在预防具有重要意义，因此对其进行检测具有决定性意义，并被视为一种护理标准。聚（ADP-核糖）聚合酶（PARP）抑制剂的维持治疗通过诱导合成致死作用，显著改善了具有 BRCA 突变和同源重组缺陷肿瘤的患者的无进展生存期。在瑞士，这些药物仅被批准用于这些患者。因此，在患者接受辅助化疗时尽早进行检测至关重要。本研究旨在确定对于新诊断的 IIIA-IVB 期（国际妇产科联合会（FIGO）分期）高级别浆液性卵巢癌患者，在瑞士，与所有患者在诊断时进行体细胞肿瘤分析相比，进行遗传咨询，然后进行同源重组缺陷检测，是否能够在 8 周内启动维持治疗，以及在日常实践中是否具有成本效益。
这是一项单中心回顾性研究，纳入了 2020 年 12 月至 2022 年 12 月期间诊断为 IIIA-IVB 期（FIGO 分期）的 44 例新诊断的高级别浆液性卵巢癌患者。该研究收集了遗传咨询、胚系 BRCA 及其他同源重组修复基因突变检测、体细胞基因 Genevat 同源重组缺陷检测的结果。检测启动维持治疗的延迟、每位患者的总检测成本和无进展生存期，以评估在临床实践中的可行性和成本效益。
44 例新诊断卵巢癌患者中，37 例（84%）接受了咨询，其中 34 例（77%）接受了胚系 BRCA 及其他同源重组修复基因突变检测。发现 5 例（15%）BRCA 突变和 3 例（9%）其他同源重组缺陷突变。其余 26 例患者中有 11 例（42%）肿瘤具有体细胞同源重组缺陷。启动维持治疗的平均时间为 5.2 周，与市场授权研究（SOLO1、PAOLA 和 PRIMA）的时间相当。每位患者的平均检测成本为 3880 瑞士法郎（瑞士法郎），如果所有患者都使用 myChoice CDx 检测在诊断时进行检测，则为 5624 瑞士法郎（p<0.0001）。
使用遗传咨询来征得新诊断卵巢癌患者的同意进行胚系检测符合国际金标准。随后的体细胞同源重组缺陷分析是对检测的补充，并确定了更多将从 PARP 抑制剂维持治疗中获益的患者。与之前的健康成本模型研究相反，该程序不会增加瑞士人群的检测成本，也不会延迟维持治疗。因此，所有患者都应接受初步的胚系分析。未来的挑战将是确保有足够的资源来迅速进行遗传咨询和胚系检测。
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