Nordic Society of Gynaecological Oncology (NSGO) and Department of Oncology Rigshospitalet-Copenhagen University Hospital, Copenhagen, Denmark.
Nordic Society of Gynaecological Oncology (NSGO) and Department of Oncology, Linköping University Hospital, Linköping, Sweden.
Cancer Res Commun. 2022 Nov 15;2(11):1436-1444. doi: 10.1158/2767-9764.CRC-22-0240. eCollection 2022 Nov.
In this analysis, we examined the relationship between progression-free survival (PFS) and mutation status of 18 homologous recombination repair (HRR) genes in patients in the non-germline -mutated (non-gm) cohort of the ENGOT-OV16/NOVA trial (NCT01847274), which evaluated niraparib maintenance therapy for patients with recurrent ovarian cancer. This exploratory biomarker analysis was performed using tumor samples collected from 331 patients enrolled in the phase III ENGOT-OV16/NOVA trial's non-gm cohort. Niraparib demonstrated PFS benefit in patients with either somatic mutated (sm; HR, 0.27; 95% confidence interval, CI, 0.08-0.88) or wild-type (wt; HR, 0.47; 95% CI, 0.34-0.64) tumors. Patients with wt tumors with other non- HRR mutations also derived benefit from niraparib (HR, 0.31; 95% CI, 0.13-0.77), as did patients with wt/HRRwt (HRR wild-type) tumors (HR, 0.49; 95% CI, 0.35-0.70). When patients with wt/HRRwt tumors were further categorized by genomic instability score (GIS), clinical benefit was observed in patients with homologous recombination-deficient (GIS ≥ 42; HR, 0.33; 95% CI, 0.18-0.61) and in patients with homologous recombination-proficient (HRp; GIS < 42; HR, 0.60; 95% CI, 0.36-0.99) disease. Although patients with sm, other non- HRR mutations, or GIS ≥ 42 benefited the most from niraparib treatment, PFS benefit was also seen in HRp (GIS < 42) patients without HRR mutations. These results support the use of niraparib in patients with recurrent ovarian cancer regardless of /HRR mutation status or myChoice CDx GIS.
We retrospectively evaluated the mutational profile of HRR genes in tumor samples from 331 patients from the non-germline -mutated cohort of the phase III NOVA trial of patients with platinum-sensitive high-grade serous ovarian cancer. Patients with non- HRR mutations generally benefited from second-line maintenance treatment with niraparib compared with placebo.
在这项分析中，我们研究了非胚系突变（非 gm）队列患者中无进展生存期（PFS）与 18 个同源重组修复（HRR）基因突变状态之间的关系，该队列来自 ENGOT-OV16/NOVA 试验（NCT01847274）的患者，该试验评估了尼拉帕利维持治疗复发性卵巢癌患者。这项探索性生物标志物分析使用来自 331 名参加 III 期 ENGOT-OV16/NOVA 试验非 gm 队列的患者的肿瘤样本进行。尼拉帕利为体细胞突变（sm；HR，0.27；95%置信区间，CI，0.08-0.88）或野生型（wt；HR，0.47；95%CI，0.34-0.64）肿瘤患者提供了 PFS 获益。wt 肿瘤伴其他非 HRR 突变的患者也从尼拉帕利治疗中获益（HR，0.31；95%CI，0.13-0.77），wt/HRRwt（HRR 野生型）肿瘤患者也获益（HR，0.49；95%CI，0.35-0.70）。当 wt/HRRwt 肿瘤患者进一步按基因组不稳定性评分（GIS）分类时，同源重组缺陷（GIS ≥ 42；HR，0.33；95%CI，0.18-0.61）和同源重组功能正常（HRp；GIS < 42；HR，0.60；95%CI，0.36-0.99）疾病患者观察到临床获益。尽管 sm、其他非 HRR 突变或 GIS ≥ 42 的患者从尼拉帕利治疗中获益最多，但 HRp（GIS < 42）无 HRR 突变的患者也观察到 PFS 获益。这些结果支持无论 HRR 突变状态或 MyChoice CDx GIS 如何，在复发性卵巢癌患者中使用尼拉帕利。
我们回顾性评估了来自 III 期 NOVA 试验铂类敏感高级别浆液性卵巢癌患者非胚系突变队列的 331 名患者的肿瘤样本中 HRR 基因的突变谱。与安慰剂相比，非 HRR 突变的患者通常从二线维持治疗尼拉帕利中获益。
