Homologous recombination deficiency and VEGF expression are key pathways in high-grade ovarian cancer. Recently, three randomized practice changing trials were published: the PAOLA-1, PRIMA and VELIA trials. The use of PARP inhibitors (PARPi) following chemotherapy has become standard of care in first line. Combination of PARPi with anti-angiogenic agents has demonstrated synergistic activity in preclinical study. This review summarizes the body of evidence supporting the efficacy and safety of the combination of PARPi and anti-angiogenic drugs in first-line homologous recombination deficiency high-grade ovarian cancer leading to US FDA and EMA approvals. This double maintenance is supported by: a large benefit with bevacizumab + olaparib compared with olaparib alone, a rationale for additive effect, and a good safety and cost-effective profile.
Keywords: PARP inhibitors; anti-angiogenic drugs; gynecologic/ovarian.
Lay abstract Ovarian cancers often present difficulties to repair their DNA and are highly vascularized tumors. Recently, three randomized practice changing trials were published: the PAOLA-1, PRIMA and VELIA trials. They use one type of therapy to target the difficulty of ovarian cancer to repair their DNA which is called poly(ADP-ribose) polymerase inhibitor. This type of therapy has become standard of care after chemotherapy. In this review, we discuss the advantage of combining anti-angiogenic agents to poly(ADP-ribose) polymerase inhibitors to target the fact that tumors are highly vascularized. First, data from laboratory suggest synergistic activity of the combination. Then, clinical data are also in favor of the combination due to additive efficacy, and a good safety and cost-effective profile.