为晚期 I 型上皮性卵巢癌（EOC）患者进行基因匹配治疗。
Genotype-matched treatment for patients with advanced type I epithelial ovarian cancer (EOC).
机构信息
Department of Medicine, Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
Department of Pathology and Laboratory Medicine, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
出版信息
Gynecol Oncol. 2017 Feb;144(2):250-255. doi: 10.1016/j.ygyno.2016.12.002. Epub 2017 Jan 3.
BACKGROUND
Genomic alterations that activate the MAPK signaling pathway frequently occur in Type I Epithelial Ovarian Cancers (EOCs). We evaluated therapeutic response outcomes in patients with type I EOC treated with genotype-matched therapy on clinical trials enrolled in a prospective molecular profiling program.
MATERIAL AND METHODS
Formalin fixed paraffin embedded tumor tissues were prospectively screened for genomic alterations using MALDI-ToF mass-spectrometry platform or targeted sequencing using the Illumina MiSeq TruSeq Amplicon Cancer Panel. Treatment outcomes on genotype-matched trials were retrospectively reviewed using RECIST version 1.1 and Gynecological Cancer Intergroup CA125 related-response criteria RESULTS: 55 patients with type I EOC underwent molecular profiling, 41 (75%) low grade serous (LGS), 9 (16%) clear cell (CC), and 5 (9%) mucinous (MC) histologies. Thirty-five patients (64%) were found to have ≥1 somatic mutations: 23 KRAS, 6 NRAS, 5 PIK3CA, 2 PTEN, 1 BRAF, 1 AKT, 1 TP53, and 1 CTNNB1. Fifteen patients were subsequently enrolled in genotype-matched phase I or II trials, including 14 patients with KRAS/NRAS mutations treated with MEK inhibitor targeted combinations. Among 14 RECIST evaluable patients, there were 7 partial responses (PR), 7 stable disease (SD) and 1 disease progression (PD). CA125 responses were observed in 10/10 evaluable KRAS/NRAS mutant patients treated with MEK inhibitor combinations CONCLUSIONS: Genotyping and targeted sequencing of Type I EOCs frequently identifies actionable mutations. Matched treatment with MEK-based combination therapy in KRAS and/or NRAS mutant type I EOC patients is an active therapeutic strategy.
背景
MAPK 信号通路的基因组改变在 I 型上皮性卵巢癌（EOC）中经常发生。我们评估了在前瞻性分子分析计划中入组的临床试验中，接受基因匹配治疗的 I 型 EOC 患者的治疗反应结果。
材料和方法
使用 MALDI-ToF 质谱平台或靶向测序对福尔马林固定石蜡包埋的肿瘤组织进行前瞻性筛选，使用 Illumina MiSeq TruSeq Amplicon Cancer Panel。使用 RECIST 版本 1.1 和妇科癌症协作组 CA125 相关反应标准，回顾性评估基因匹配试验的治疗结果。
结果
55 例 I 型 EOC 患者进行了分子分析，41 例（75%）为低级别浆液性（LGS），9 例（16%）为透明细胞（CC），5 例（9%）为黏液性（MC）组织学。35 例患者（64%）发现有≥1 个体细胞突变：23 例 KRAS，6 例 NRAS，5 例 PIK3CA，2 例 PTEN，1 例 BRAF，1 例 AKT，1 例 TP53 和 1 例 CTNNB1。随后有 15 例患者入组基因匹配的 I 期或 II 期试验，包括 14 例 KRAS/NRAS 突变患者接受 MEK 抑制剂靶向联合治疗。在 14 例可评估 RECIST 的患者中，有 7 例部分缓解（PR），7 例疾病稳定（SD）和 1 例疾病进展（PD）。在接受 MEK 抑制剂联合治疗的 10/10 可评估 KRAS/NRAS 突变患者中观察到 CA125 反应。
结论
I 型 EOC 的基因分型和靶向测序经常发现可操作的突变。在 KRAS 和/或 NRAS 突变的 I 型 EOC 患者中，用 MEK 为基础的联合治疗进行匹配治疗是一种积极的治疗策略。
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