Salvage chemotherapy and maintenance therapy with poly adenosine diphosphate-ribose polymerase inhibitors for bevacizumab-resistant relapse of epithelial ovarian cancer

Adjuvant chemotherapy combined with bevacizumab, an angiogenesis inhibitor, can improve the survival of advanced epithelial ovarian cancer (EOC), but relapse during bevacizumab maintenance therapy may occur. Despite poly adenosine ribosepolymerase (PARP) inhibitors were shown to achieve remission in the relapsed patients upon salvage chemotherapy and long-term maintenance, there is little evidence on their efficacy or criteria for selecting bevacizumab-resistant recurrent EOC patients who would benefit from PARP inhibitors. In this single-center, retrospective, case-series study, we evaluated the efficacy, safety and selection criteria for salvage chemotherapy followed by PARP inhibitors in bevacizumab-resistant EOC patients who recurred during bevacizumab maintenance. The primary endpoint was post-progression survival (PPS), and the secondary endpoints were progression-free survival (PFS) and safety. In all, the data of 49 EOC patients, most of whom were graded as stage III (91.8%) with high-grade serous histology (81.6%), were assessed. They were classified into three groups based on platinum-free interval (PFI) and response to salvage chemotherapy: platinum-based chemotherapy followed by PARP inhibitors, platinum-based chemotherapy followed by non-PARP inhibitors, and non-platinum-based chemotherapy. Survival analysis showed the median PFS and median PPS for the platinum-based chemotherapy followed by PARP inhibitors group were 326 and 771 days, which were significantly longer than the other groups. The highly platinum-sensitive relapse (PSR) group (PFI >12 months) achieved prolonged PPS, while there was no relationship between the clinical status on salvage chemotherapy and response to PARP inhibitors. Adverse events during PARP inhibitor led to withdrawal and dose reduction in >40% of patients; however, no patients discontinued the drugs. Altogether, the study results showed that maintenance therapy using PARP inhibitor was effective and feasible for patients selected based on platinum sensitivity from bevacizumab-resistant relapsed EOC. PFI after adjuvant chemotherapy could predict bevacizumab-resistant EOC patients' response to PARP inhibitors, which might be effective despite therapeutically insufficient salvage chemotherapy.