Elsevier

Annals of Oncology

Volume 31, Issue 9, September 2020, Pages 1148-1159
Annals of Oncology

Review
The forefront of ovarian cancer therapy: update on PARP inhibitors

https://doi.org/10.1016/j.annonc.2020.06.004Get rights and content
Under an Elsevier user license
open archive

Highlights

  • In four phase III trials in ovarian cancer, front-line PARP inhibition significantly improved progression-free survival.

  • Differences in trial design, patient selection and primary analysis population influence interpretation of these trials.

  • PARP inhibitors play a pivotal role in managing newly diagnosed ovarian cancer, affecting subsequent treatment choices.

  • Priorities include refining testing and identifying therapies for patients benefiting less from PARP inhibition.

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.

Key words

PARP inhibitor
ovarian cancer
olaparib
niraparib
veliparib
phase III

Cited by (0)