Wednesday 4th December 2019
Addressing unmet needs in ovarian cancer
Ovarian cancer is the 5th worldwide leading cause of death in women due to cancer, with more than 70% of cases diagnosed at an advanced stage.
Standard front-line treatment for advanced ovarian cancer has, for many years, remained cytoreductive surgery with the goal of no residual disease, followed by the combination of platinum- and taxane-based chemotherapy. However, the landscape of ovarian cancer treatment is complicated by the heterogeneity of the different tumour histological types, each with their own distinct cellular origin, mutational spectrum, and thus, prognosis. As a result, the majority of patients relapse on platinum-based chemotherapy. This significant disease burden has been addressed in recent years by the development of several new diagnostic and therapeutic approaches.
Numerous studies have reported that mutation in BRCA1 or BRCA2 is a prognostic marker in ovarian cancer and that patients with a BRCA mutation, especially BRCA2, have better survival outcomes, which is likely to reflect increased response rates to platinum-based chemotherapy. As a result, testing for BRCA1/2 mutations is recommended for all patients with ovarian cancer.
Bevacizumab, which is an antivascular epithelial growth factor (anti-VEGF) monoclonal antibody, has demonstrated improve survival in patients with ovarian cancer when added to first-line platinum-based chemotherapy. As a result it was the first targeted therapy to receive approval from the European Medicines Agency (EMA) for the treatment of epithelial ovarian cancer in the first-line and relapsed settings.
Poly-ADP ribose polymerases (PARPs) are enzymes that transfer ADP-ribose groups to target proteins. They function in cellular signalling pathways, including DNA repair, transcriptional regulation, RNA interference, mitochondrial function, formation of subnuclear bodies and in cell division. PARP inhibitors have been shown to lead to a cycle of DNA damage in ovarian cancer cells, ultimately resulting in cell cycle arrest or death. Several PARP inhibitors have been evaluated as monotherapy, combination therapy and as maintenance treatment following response to platinum-based chemotherapy in ovarian cancer. Olaparib was the first PARP inhibitor approved by the European and American regulatory agencies for ovarian cancer. Subsequently, niraparib and rucaparib were also approved. PARP inhibitors have the greatest activity in patients with BRCA1/2 mutations.
There are also several new drugs still under development in ongoing clinical trials, including immunotherapy, which is aimed at enhancing an individual’s own immune system to eliminate tumour cells.