Tuninetti Valentina, Ghisoni Eleonora, Pignata Sandro, Picardo Elisa, Raspagliesi Francesco, Andreetta Claudia, Maldi Elena, Artioli Grazia, Mammoliti Serafina, Zanchi Lucia, Sikokis Angelica, Biglia Nicoletta, Parisi Alessandro, Mandato Vincenzo Dario, Carella Claudia, Cormio Gennaro, Marinaccio Marco, Puppo Andrea, Paolini Biagio, Borsotti Lucia, Scotto Giulia, Turinetto Margherita, Sangiolo Dario, Di Maio Massimo, Valabrega Giorgio
Department of Oncology, University of Turin, Ordine Mauriziano Hospital, 10128 Turin, Italy.
Department of Oncology, Immuno-Oncology Service, University Hospital of Lausanne-CHUV, 1011 Lausanne, Switzerland.
Cancers (Basel). 2023 Feb 6;15(4):1032. doi: 10.3390/cancers15041032.
There is compelling need for novel biomarkers to predict response to PARP inhibitors (PARPi) in BRCA wild-type (WT) ovarian cancer (OC).
MITO 37 is a multicenter retrospective study aiming at correlating Ki67 expression at diagnosis with a clinical outcome following platinum treatment and PARPi maintenance. Clinical data were collected from high grade serous or endometroid BRCAWT OC treated with niraparib or rucaparib maintenance between 2010-2021 in 15 centers. Ki67 expression was assessed locally by certified pathologists on formalin-fixed paraffin embedded (FFPE) tissues. Median Ki67 was used as a cut-off.
A total of 136 patients were eligible and included in the analysis. Median Ki67 was 45.7% (range 1.0-99.9). The best response to platinum according to median Ki67 was 26.5% vs. 39.7% complete response (CR), 69.1% vs. 58.8% partial response (PR), 4.4% vs. 1.5% stable disease (SD). The best response to PARPi according to median Ki67 was 19.1% vs. 36.8% CR, 26.5% vs. 26.5% PR, 26.5 vs. 25% SD, 27.9% vs. 16.2% progressive disease (PD). No statistically significant differences in progression free survival (PFS) and overall survival (OS) were identified between low and high Ki67. PFS and OS are in line with registration trials.
Ki67 at diagnosis did not discriminate responders to PARPi.
对于预测BRCA野生型（WT）卵巢癌（OC）对PARP抑制剂（PARPi）的反应，迫切需要新的生物标志物。
MITO 37是一项多中心回顾性研究，旨在将诊断时的Ki67表达与铂类治疗及PARPi维持治疗后的临床结局相关联。收集了2010年至2021年期间在15个中心接受尼拉帕利或鲁卡帕利维持治疗的高级别浆液性或子宫内膜样BRCA WT OC的临床数据。Ki67表达由认证病理学家在福尔马林固定石蜡包埋（FFPE）组织上进行局部评估。以Ki67中位数作为临界值。
共有136例患者符合条件并纳入分析。Ki67中位数为45.7%（范围1.0 - 99.9）。根据Ki67中位数，铂类治疗的最佳反应为完全缓解（CR）26.5%对39.7%，部分缓解（PR）69.1%对58.8%，疾病稳定（SD）4.4%对1.5%。根据Ki67中位数，PARPi治疗的最佳反应为CR 19.1%对36.8%，PR 26.5%对26.5%，SD 26.5%对25%，疾病进展（PD）27.9%对16.2%。低Ki67和高Ki67之间在无进展生存期（PFS）和总生存期（OS）方面未发现统计学显著差异。PFS和OS与注册试验结果一致。
诊断时的Ki67不能区分对PARPi的反应者。
