|PARP inhibitors in advanced ovarian cancer|
Poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors keep PARP remaining at DNA sites with single-strand breaks, which subsequently inhibits the repair of the single-strand breaks. As double-strand breaks cannot be fixed in tumours where homologous recombination repair is impaired, these tumour cells with accumulated DNA damage will eventually die. Based on the above findings, olaparib, a PARP inhibitor, has been approved in the US and Europe as maintenance treatment for those who have recurrent ovarian cancer that was sensitive to platinum in the most recent round of chemotherapy. It has also been approved for ovarian cancer patients with a deleterious or suspected deleterious germline BRCA mutation who have been in three or more lines of chemotherapy. It has been recommended by the NCCN that maintenance therapy with a PARP inhibitor should be considered in recurrent ovarian cancer patients who have been sensitive to platinum regardless of BRCA mutation.
Here in this phase 3 trial (the SOLO1 trial, here in NEJM), the team led by Dr. Moore reported the efficacy of maintenance therapy with olaparib in those with advanced ovarian cancer with a germline or somatic mutation in BRCA1/2 genes who have been sensitive to platinum. After completion of platinum-based chemotherapy, patients were randomly assigned to two groups: the olaparib group that had 260 patients receiving olaparib 300 mg twice daily, and the placebo group that had 130 patients. The primary end point was progression-free survival. Patients in the olaparib group had longer progression-free survival, which was approximately 36 months longer than that of the placebo group. At 3 years after completion of chemotherapy, the rate of freedom from disease progression or death was 60% in the olaparib group, compared to 27% in the placebo group (hazard ratio, 0.30; 95% CI, 0.23-0.41, p<0.001). No new adverse events related to olaparib were reported.
This report extends the application of PARP inhibitors to advanced ovarian cancer patients with BRCA1/2 mutations as maintenance treatment from previous administration in recurrent ovarian cancer patients.
This study was supported by pharmaceutical companies.