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Debate 17B - When is the Best Time to Use PARP Inhibitors for Maintenance?

First Recurrence

from Section III - Ovarian Cancer

Published online by Cambridge University Press:  20 July 2023

Dennis S. Chi
Affiliation:
Memorial Sloan-Kettering Cancer Center, New York
Nisha Lakhi
Affiliation:
Richmond University Medical Center, Staten Island
Nicoletta Colombo
Affiliation:
University of Milan-Bicocca
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Summary

Poly ADP ribose polymerase (PARP) inhibitors have led to a step change in the management of advanced ovarian cancer following the first approval of these inhibitors in 2014. PARP is an enzyme needed for DNA repair and its inhibition results in the accumulation of single-strand DNA breaks. PARP inhibitors were initially hypothesized to have maximum efficacy in ovarian cancer with BRCA1/2 mutations or homologous recombination (HR) deficiency (HRD) ) given the role of these pathways in repairing double-stranded DNA breaks. The accumulation of both single-strand and double-strand breaks would result in synthetic lethality and preferential cancer cell cytotoxicity with BCRA1/2 mutations and HRD being a predictive biomarker of response. Here we present data that patients with recurrent ovarian cancer will benefit from PARP inhibitors, given as maintenance therapy irrespective of BRCA or HR status. This has been shown with olaparib, niraparib, and rucaparib; all three PARP inhibitors are licensed for the treatment of recurrent ovarian cancer following a response to platinum-based therapy in both BRCA-mutant and wild-type patients.

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Chapter
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Publisher: Cambridge University Press
Print publication year: 2023

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References

Ledermann, J, et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med 2012;366(15):13821392.CrossRefGoogle ScholarPubMed
Friedlander, M, et al. Long-term efficacy, tolerability and overall survival in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer treated with maintenance olaparib capsules following response to chemotherapy. Br J Cancer 2018;119(9):10751085.CrossRefGoogle ScholarPubMed
Pujade-Lauraine, E, et al. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol 2017;18(9):12741284.CrossRefGoogle Scholar
Mirza, MR, et al. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med 2016;375(22):21542164.CrossRefGoogle ScholarPubMed
Coleman, RL, et al. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017;390(10106):19491961.CrossRefGoogle ScholarPubMed

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