The forefront of ovarian cancer therapy: update on PARP inhibitors
- PMID: 32569725
- DOI: 10.1016/j.annonc.2020.06.004
The forefront of ovarian cancer therapy: update on PARP inhibitors
Erratum in
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Corrigendum to 'The forefront of ovarian cancer therapy: update on PARP inhibitors': [Annals of Oncology 31 (2020) 1148-1159].Ann Oncol. 2021 Aug;32(8):1066-1067. doi: 10.1016/j.annonc.2021.05.796. Epub 2021 Jun 2. Ann Oncol. 2021. PMID: 34090767 No abstract available.
Abstract
Background: In recurrent ovarian cancer, poly(ADP-ribose) polymerase (PARP)-inhibiting agents have transformed the treatment of platinum-sensitive disease. New data support use of PARP inhibitors earlier in the treatment algorithm.
Design: We review results from recent phase III trials evaluating PARP inhibitors as treatment and/or maintenance therapy for patients with newly diagnosed ovarian cancer. We discuss the efficacy and safety of these agents in the all-comer and biomarker-selected populations studied in clinical trials, and compare the strengths and limitations of the various trial designs. We also consider priorities for future research, with a particular focus on patient selection and future regimens for populations with high unmet need.
Results: Four phase III trials (SOLO-1, PAOLA-1/ENGOT-OV25, PRIMA/ENGOT-OV26 and VELIA/GOG-3005) demonstrated remarkable improvements in progression-free survival with PARP inhibitor therapy (olaparib, niraparib or veliparib) for newly diagnosed ovarian cancer. Differences in trial design (treatment and/or maintenance setting; single agent or combination; bevacizumab or no bevacizumab), patient selection (surgical outcome, biomarker eligibility, prognosis) and primary analysis population (intention-to-treat, BRCA mutated or homologous recombination deficiency positive) affect the conclusions that can be drawn from these trials. Overall survival data are pending and there is limited experience regarding long-term safety.
Conclusions: PARP inhibitors play a pivotal role in the management of newly diagnosed ovarian cancer, which will affect subsequent treatment choices. Refinement of testing for patient selection and identification of regimens to treat populations that appear to benefit less from PARP inhibitors are a priority.
Keywords: PARP inhibitor; niraparib; olaparib; ovarian cancer; phase III; veliparib.
Copyright © 2020 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.
Conflict of interest statement
Disclosure MRM has received fees for serving on advisory boards from Tesaro, Clovis Oncology and AstraZeneca and speaker fees from AstraZeneca, Tesaro and Roche. RLC reports research funding from Abbott/AbbVie, Array BioPharma, AstraZeneca/MedImmune, Clovis Oncology, Esperance Pharmaceuticals, Johnson & Johnson, Merck, OncoMed and Roche/Genentech, consultancy/advisory roles for Clovis Oncology, Esperance Pharmaceuticals and Genentech/Roche and travel/accommodation/expenses from Amgen, Array BioPharma, AstraZeneca/MedImmune, Bayer, Clovis Oncology, GOG-Foundation, Research to Practice, Merck, Millennium, Roche/Genentech, New Mexico Cancer Center, University of California, Irvine, University of Cincinnati Cancer Center and University of Miami. AGM reports research funding from Roche and GSK and fees for serving on advisory boards from Amgen, AstraZeneca, Clovis, Genmab, GSK, Immunogen, Merck, MSD, Oncoinvent and Roche. KNM reports research funding from PTC Therapeutics, Lilly, Merck, Genentech/Roche, Immunogen, AbbVie, AstraZeneca, GSK/Tesaro and OncoMed and consultancy/advisory roles for Aravive, AstraZeneca, Clovis, Eisai, GSK/Tesaro, Genentech/Roche, Immunogen, Merck, Mersana, OncoMed/Mereo, VBL Therapeutics, Vavotar and Tarveda. NC reports research funding from AstraZeneca and Roche, consulting fees and travel support from PharmaMar, and consulting fees from AstraZeneca, GSK/Tesaro, Clovis, Immunogen, MSD, Pfizer and Biocad. IR-C reports consulting fees and travel support from Roche and AstraZeneca, consulting fees from PharmaMar, Genmab, Pfizer, Merck, AbbVie, Tesaro/GSK and Clovis, and grant support and consulting fees from MSD. SP reports honoraria from AstraZeneca, MSD, Tesaro/GSK, Clovis, PharmaMar, Pfizer and Roche and research funding from MSD, AstraZeneca, Roche and Pfizer.
