Impatto Delle Diverse Varianti Dei Geni BRCA1/2 su Risposta Alla Terapia e Prognosi Del Carcinoma Ovarico
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- Differences in BRCA1/2 status for predictive response to chemotherapy
研究概览
简要总结
Identify any significant differences in terms of drug response and survival between the different possible alterations in the BRCA1/2 genes, in order to stratify ovarian cancer patients with a view to increasingly personalised and thus effective therapy.
详细描述
Ovarian carcinoma (OC) is the leading cause of death among gynaecological neoplasms. It is, in fact, a neoplasm that is not very frequent but highly lethal: in Emilia-Romagna, the incidence is about 17 cases per 100,000 inhabitants and the mortality rate is around 15 cases per 100,000, with a very high mortality/incidence ratio (0.83). The high mortality rate is mainly due to the fact that, due to the non-specific and late symptoms, 75-80% of patients arrive at the diagnosis at an advanced stage of the disease (III-IV), characterised by a 5-year survival of less than 25%.
The primary therapeutic approach for this tumour is a combination of debulking surgery and platinum-based chemotherapy generally associated with taxanes, while as far as maintenance therapies are concerned, PARP inhibitors (PARPi), drugs capable of blocking a DNA repair mechanism alternative to that of homologous recombination, have been gaining in importance in recent years. They have proved particularly effective in tumours that present alterations in the BRCA1 and BRCA2 genes, which are key players in homologous recombination. For this reason, the detection of mutations in the BRCA1 and BRCA2 genes is predictive of the efficacy of PARPi maintenance therapy and, consequently, as of 2015, the BRCA test has been indicated in all women newly diagnosed with ovarian cancer (excluding borderline and mucinous forms), possibly from tumour tissue, given the evidence that in addition to constitutional (inherited) variants, somatic variants (acquired and tumour-confined), present in about 9%, are also associated with a PARPi benefit.
Recent data, however, have challenged the assumption that functionally significant variants for which a predisposing role has been demonstrated for hereditary breast and ovarian cancers are necessarily predictive of drug response. Furthermore, the fact that somatic mutations are present in only a limited fraction of the DNA copies analysed in a tumour suggests that there may be residual BRCA activity that compromises effective PARPi activity.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •ovarian cancer diagnosis by 31/12/2021;
- •BRCA test at the UOC of Medical Genetics of the IRCCS AOU of Bologna Policlinico S.Orsola by 31/12/2021;
- •follow-up and/or treatment at Medical Oncology and/or Gynaecological Oncology of the IRCCS Azienda Ospedaliero-Universitaria (AOU) of Bologna for a period of time of at least 1 year and by 31/12/2021 and for a minimum period of 6 months
排除标准
- •ovarian carcinoma of 'mucinous' or 'borderline' histotype.
结局指标
主要结局
Differences in BRCA1/2 status for predictive response to chemotherapy
时间窗: 12 months
The primary objective of the study is to clarify whether differences in the status of BRCA1/2 (presence/absence of germline and/or somatic) may be predictive in the response to chemotherapy and survival of patients with ovarian cancer.
次要结局
- Differences in response to chemotherapy based on BRCA variant(12 months)