At present, surgery and cytotoxic chemotherapy remain the main treatment methods for ovarian cancer. Seventy percent of ovarian cancer patients are diagnosed at an advanced stage of disease due to the insidious nature of ovarian cancer and the ineffectiveness of screening tests for early detection ( Henderson et al., 2018). This review further poses an interesting topic: the efficacy and safety in patients retreated with PARPis after previous PARPi treatment-“PARPi after PARPi”.
#Hrd positive ovarian cancer trial
This review mainly summarizes the latest clinical trial results and combination treatment of PARPis in ovarian cancer with non-BRCA mutations, and discusses the application prospects, including optimizing combination therapy against drug resistance, developing unified and accurate HRD status detection methods for patient selection and stratification. Therefore, the development of reliable HRD status detection methods to determine the beneficiary population, as well as rational combination treatment are warranted. The reversal of homologous recombination (HR) function during the treatment will not only cause resistance to PARPis, but also reduce the accuracy of the current method to determine HRD status. However, lack of unified HRD status detection method poses a challenge for the accurate selection of PARPi beneficiaries. Although BRCA mutated population are still the main beneficiaries of PARPi, recent clinical trials indicated PARPis’ therapeutic potential in non-BRCA mutated population, especially in homologous recombination repair deficiency (HRD) positive population. With the incremental results from new clinical trials, the applicable population of PARPi for ovarian cancer have expanded to population with non-BRCA mutations. The three PARPis currently approved by the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of ovarian cancer are Olaparib, Niraparib and Rucaparib.
Poly ADP-ribose polymerase inhibitor (PARPi) has become an important maintenance therapy for ovarian cancer after surgery and cytotoxic chemotherapy, which has changed the disease management model of ovarian cancer, greatly decreased the risk of recurrence, and made the prognosis of ovarian cancer better to certain extent. Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China.