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Debate 16B - What is the Best Front-line Maintenance Therapy for HRD-positive Ovarian Cancer?

Bevacizumab plus PARP inhibitor

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

Two classes of targeted therapies have revealed a progression-free survival prolongation in front-line maintenance in epithelial high-grade ovarian carcinomas: bevacizumab and poly(ADP-ribose) polymerases inhibitors (PARPi). PARPi have demonstrated particular efficacy in patients having BRCA1/2 mutations, or other homologous-recombination repair deficiency (HRD). To date, the question of single maintenance with PARPi versus double maintenance with PARPi + bevacizumab has not been specifically addressed. Three trials (SOLO-1, PRIMA, VELIA) compared PARPi versus placebo without any bevacizumab, and a fourth (PAOLA-1) utilized bevacizumab plus placebo as the control arm comparing it to bevacizumab plus PARPi. In the following article, we support a double maintenance approach with PARPi + bevacizumab in the HRD-positive subgroup based on (i) a never-reached efficiency in this subgroup with bevacizumab+olaparib,better than olaparib alone in a patient-adjusted indirect comparison (ii) a rationale for additive effected (iii) a good safety and cost-effective profile. The FDA and EMA indeed approved double maintenance for HRD-positive patients in 2020.

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Publisher: Cambridge University Press
Print publication year: 2023

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References

González Martín, A, et al. Exploratory outcome analyses according to stage and/or residual disease in the ICON7 trial of carboplatin and paclitaxel with or without bevacizumab for newly diagnosed ovarian cancer. Gynecol Oncol 2019;152:5360.CrossRefGoogle ScholarPubMed
González-Martín, A, et al. Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 2019;381:23912402.CrossRefGoogle ScholarPubMed
Coleman, RL, et al. Veliparib with first-line chemotherapy and as maintenance therapy in ovarian cancer. N Engl J Med 2019;381:24032415.CrossRefGoogle ScholarPubMed
Moore, K, et al. Maintenance olaparibin patients with newly diagnosed advanced ovarian cancer. N Engl J Med 2018;379:24952505.CrossRefGoogle ScholarPubMed
Ray-Coquard, I, et al. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. N Engl J Med 2019;381:24162428.CrossRefGoogle ScholarPubMed
Vergote, I, et al. Population-adjusted indirect treatment comparison of the SOLO1 and PAOLA-1/ENGOT-ov25 trials evaluating maintenance olaparibor bevacizumab or the combination of both in newly diagnosed, advanced BRCA-mutated ovarian cancer. Eur J Cancer 2021;157:415423. https://doi.org/10.1016/j.ejca.2021.08.023CrossRefGoogle ScholarPubMed

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