The forefront of ovarian cancer therapy: update on PARP inhibitors.
PARP inhibitor
niraparib
olaparib
ovarian cancer
phase III
veliparib
Journal
Annals of oncology : official journal of the European Society for Medical Oncology
ISSN: 1569-8041
Titre abrégé: Ann Oncol
Pays: England
ID NLM: 9007735
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
04
03
2020
revised:
29
05
2020
accepted:
02
06
2020
pubmed:
23
6
2020
medline:
7
1
2021
entrez:
23
6
2020
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 32569725
pii: S0923-7534(20)39891-4
doi: 10.1016/j.annonc.2020.06.004
pii:
doi:
Substances chimiques
Poly(ADP-ribose) Polymerase Inhibitors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1148-1159Commentaires et corrections
Type : ErratumIn
Informations de copyright
Copyright © 2020 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
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.