Homologous recombination repair deficiency (HRD) testing in newly diagnosed advanced-stage epithelial ovarian cancer: A Belgian expert opinion

Abstract

Ovarian cancer (OC) has a poor prognosis as most patients present with non-specific symptoms and the disease is mostly diagnosed at advanced stages. Approximately 90% of cases are classified as epithelial OC (EOC), a category comprising histologically and molecularly distinct tumours. Identifying reliable biomarkers and employing personalised therapies in OC subgroups is crucial for battling the disease. EOCs are often characterised by homologous recombination repair deficiency (HRD), frequently caused by inactivation of the breast cancer susceptibility (BRCA) genes. These findings have led to the development of poly- (adenosine diphosphate [ADP])- ribose polymerase inhibitors (PARPi), which are synthetically lethal to HRD tumour cells. Both patients with HRD and non-HRD tumours can benefit from PARPi therapy in the recurrent setting. Moreover, recent phase III trials in patients with newly diagnosed advanced-stage OC have demonstrated greater clinical benefit from PARPi in treating HRD than non-HRD tumours. These findings offer new opportunities for the use of PARPi as maintenance therapy after first-line chemotherapy based on the presence of HRD. In the current article, we provide recommendations for HRD testing and treatment of patients with newly diagnosed advanced-stage EOC.

Comparison of the Efficacy of Cisplatin/Paclitaxel Versus Carboplatin/Paclitaxel in Improving Survival and Quality of Life in the Advanced Ovarian Cancer Patient Population: A Systematic Review and Meta-Analysis of Randomized Control Trials

“…In 2020, ovarian carcinoma was ranked as the third most prevalent cancer globally [ 23 ]. Considering the aggressively malignant nature of ovarian tumors [ 24 ], the chemotherapeutic management of advanced carcinomas after radical debulking surgery consisted of treatment with a taxane/platinum doublet [ 25 ]. For years, multiple researchers set out to answer one simple question: between carboplatin and cisplatin, which of the two was more efficacious and well-tolerated in terms of overall survival and quality of life when combined with paclitaxel?…”

Ovarian cancer is detectable from peripheral blood using machine learning over T-cell receptor repertoires

“…The disease is often diagnosed late [ 2 ] and is composed of several subtypes with distinct biological and molecular properties [ 3 ] (even within the same histological subtype [ 4 ]), with an inconsistency in availability of and access to treatment [ 5 ]. Outcomes in OC depend on timely diagnosis and access to appropriate surgery and systemic therapy [ 6 , 7 ]. OC is often diagnosed at stages III and IV, where the 5-year survival rate is only 17–39% [ 8 ].…”

Molecular and phenotypic characteristics influencing the degree of cytoreduction in high‐grade serous ovarian carcinomas

“…During the last decade, phenotypic and molecular biomarkers have been gradually introduced to direct maintenance therapy with inhibitors of poly‐ADP‐ribose polymerase (PARP) 13,14 and anti‐angiogenetic agents 15–17 for patients with advanced disease 18–20 . The tumour biological characteristics of HGSOC have been explored, resulting in the identification of at least four molecular subtypes 21,22 .…”