Rationale for combination PARP inhibitor and antiangiogenic treatment in advanced epithelial ovarian cancer: A review

Abstract

Inhibitors of poly(ADP-ribose) polymerase (PARP) and angiogenesis have demonstrated single-agent activity in women with advanced ovarian cancer. Recent studies have aimed to establish whether combination therapy can augment the response seen with PARP inhibitors or antiangiogenic agents alone. This review provides an overview of PARP inhibitors and antiangiogenics as monotherapy in women with advanced ovarian cancer, explores potential mechanisms of action of PARP inhibitor and antiangiogenic combination treatments, reviews efficacy and safety data from trials evaluating this combination, and outlines ongoing and future trials evaluating this combination, discussing these in the context of the current and future treatment landscape for women with advanced ovarian cancer. Sentinel studies evaluating PARP inhibitor (n = 8), antiangiogenic (n = 4), and combination (n = 7) therapy were identified in women with newly diagnosed (n = 7) and recurrent (n = 12) ovarian cancer. PARP inhibitors included olaparib (n = 9), niraparib (n = 4), rucaparib (n = 1), and veliparib (n = 1). Antiangiogenic agents included bevacizumab (n = 7) and cediranib (n = 4). PARP inhibitors combined with antiangiogenics demonstrated efficacy based on objective response rates and progression-free survival (PFS) in the relapsed disease setting. Maintenance therapy with the PARP inhibitor, olaparib, plus antiangiogenic therapy offered a significant PFS benefit versus the antiangiogenic alone in women with newly diagnosed advanced ovarian cancer who tested positive for homologous recombination deficiency. Combination therapy was tolerated, with no new safety signals reported compared with monotherapy trials. PARP inhibitors and antiangiogenics have changed the landscape of ovarian cancer treatment. The PARP inhibitor plus antiangiogenic combination is a novel treatment option that appears promising in the first-line advanced and recurrent ovarian cancer settings, although the role of this combination in recurrent disease requires further elucidation. Defining which patients are candidates for monotherapy or combination therapy is critical, taking into consideration safety profiles of therapies alone or in combination, and how these treatments should be sequenced in clinical practice.

Keywords: Antiangiogenic; Niraparib; Olaparib; Ovarian cancer; PARP inhibitor; Rucaparib.