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Review
. 2021 Aug;162(2):482-495.
doi: 10.1016/j.ygyno.2021.05.018. Epub 2021 Jun 3.

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

Angeles Alvarez Secord  1 , David M O'Malley  2 , Anil K Sood  3 , Shannon N Westin  3 , Joyce F Liu  4
Affiliations
Free article
Review

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

Angeles Alvarez Secord et al. Gynecol Oncol. 2021 Aug.
Free article

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.

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Conflict of interest statement

Declaration of Competing Interest AAS: reports institutional support for clinical research from AbbVie and National Cancer Trial Network; institutional support for clinical research and personal fees from Advisory Boards from AstraZeneca, Clovis Oncology, Roche/Genentech and GSK/Tesaro; and personal fees for an Advisory Board from Myriad Genetics relevant to the content in this manuscript. She has received institutional support from Amgen, Astellas Pharma Inc., Astex Pharmaceuticals Inc., Boehringer Ingelheim, Bristol-Myers Squibb Co., Eisai, Endocyte, Exelixis, Immutep Ltd., Incyte, Merck, PharmaMar, Seattle Genetics, Inc. and VBL Therapeutics; personal fees for Advisory Boards from Aravive, Cordgenics, Eisai, Janssen/Johnson & Johnson, Merck, Mersana and Oncoquest; and participated in Steering Committees (noncompensated) for Roche/Genentech and VBL Therapeutics outside the submitted work. DMOM: reports personal fees and institutional support for clinical research from AstraZeneca, Clovis, Tesaro, Immunogen, Janssen/Johnson & Johnson, Abbvie, Regeneron, Amgen, Novocure, Genentech/Roche, GOG Foundation, Eisai, Agenus, GSK and Merck; personal fees from Ambry, Myriad Genetics, and Tarveda; institutional support for clinical research from VentiRx, Array Biopharma, EMD Serono, Ergomed, Ajinomoto Inc., Ludwig Cancer Research, Stemcentrx, Inc., CERULEAN PHARMA, Bristol-Myers Squibb Co., Serono Inc., TRACON Pharmaceuticals, Yale University, New Mexico Cancer Care Alliance, INC Research, Inc., inVentiv Health Clinical, Iovance Biotherapeutics, Inc. and PRA Intl. AKS: has consulted for Merck and Kiyatec, is a shareholder in BioPath, and has received research support from M-Trap. SNW: reports personal fees for consulting from Agenus, AstraZeneca, Circulogene, Clovis Oncology, Merck, Novartis, Pfizer, Roche/Genentech, GSK/Tesaro, Eisai and Zentalis; and research funding to her institution from ArQule, AstraZeneca, Bayer, Bio-Path, Clovis Oncology, Cotinga Pharmaceuticals, Novartis, Roche/Genentech and GSK/Tesaro. JFL: reports advisory board participation for AstraZeneca, Clovis, Genentech, Merck, Regeneron and Tesaro/GSK; consulting for Genentech; and funding to her institution for study conduct as Principal Investigator on trials from 2X Oncology, Aravive, Arch Oncology, AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, CytomX Therapeutics, Genentech, GlaxoSmithKline, Regeneron, Surface Oncology, Tesaro and Vigeo Therapeutics.

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