Quantitative Analysis of the Efficacy of PARP Inhibitors as Maintenance Therapy in Recurrent Ovarian Cancer

Objective: This study aimed to establish a pharmacodynamic model and to screen reasonable covariates to quantitatively describe the efficacy of poly (ADP-ribose) polymerase inhibitors (PARPis) as maintenance treatment for recurrent ovarian cancer (ROC).Methods: The log normal hazard function model w...

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Autores principales:	Lili Gao, Rui Chen, Ting Li, Lujin Li, Qingshan Zheng
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	recurrent ovarian cancer maintenance treatment PARP pharmacodynamic model progress-free survival Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/585acc5210064b1aa454b88a24087b05
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spelling	oai:doaj.org-article:585acc5210064b1aa454b88a24087b052021-11-08T05:30:21ZQuantitative Analysis of the Efficacy of PARP Inhibitors as Maintenance Therapy in Recurrent Ovarian Cancer1663-981210.3389/fphar.2021.771836https://doaj.org/article/585acc5210064b1aa454b88a24087b052021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.771836/fullhttps://doaj.org/toc/1663-9812Objective: This study aimed to establish a pharmacodynamic model and to screen reasonable covariates to quantitatively describe the efficacy of poly (ADP-ribose) polymerase inhibitors (PARPis) as maintenance treatment for recurrent ovarian cancer (ROC).Methods: The log normal hazard function model was established by using progression-free survival (PFS) data of 1,169 patients from published randomized trials on FDA-approved PARP inhibitors (olaparib, niraparib, and rucaparib). Monte Carlo simulation was used to compare PFS values in different scenarios, such as monotherapy (administered alone) and combination therapy (PARPis combined with chemo- or target-therapies), different biomarker statuses, and different PARP inhibitors. PFS was also estimated.Results: The study showed that the median PFS was 8.5 months with monotherapy and 16.0 months with combination therapy. The median PFS of patients with the BRCA mutation, BRCA wild-type, and HRD-positivity were 11.0, 7.5, and 9.0 months in monotherapy, respectively, and 23.0, 14.0 and 17.5 months, in combination therapy, respectively. In addition, the median PFS of olaparib, niraparib, and rucaparib monotherapy were about 9.5, 10.5, and 12.0 months, respectively, and about 19.0, 20.0, and 25 months, respectively, in combination therapy. The median PFS values in combination with cediranib, bevacizumab, and chemotherapy were approximately 17.0, 12.5 and 19.5 months, respectively.Conclusion: PARPi combination therapy is more effective as maintenance treatment for ROC than monotherapy, and the efficacy of PARPis in combination with chemotherapy is higher than that of the combination with antiangiogenic drugs. We found that the PFS of BRCA wild-type was similar to that of HRD-positive patients, and there was no significant difference in PFS between olaparib, niraparib, and rucaparib, which provides necessary quantitative information for the clinical practice of PARPis in the treatment of ROC.Lili GaoRui ChenTing LiLujin LiQingshan ZhengFrontiers Media S.A.articlerecurrent ovarian cancermaintenance treatmentPARPpharmacodynamic modelprogress-free survivalTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	recurrent ovarian cancer maintenance treatment PARP pharmacodynamic model progress-free survival Therapeutics. Pharmacology RM1-950
spellingShingle	recurrent ovarian cancer maintenance treatment PARP pharmacodynamic model progress-free survival Therapeutics. Pharmacology RM1-950 Lili Gao Rui Chen Ting Li Lujin Li Qingshan Zheng Quantitative Analysis of the Efficacy of PARP Inhibitors as Maintenance Therapy in Recurrent Ovarian Cancer
description	Objective: This study aimed to establish a pharmacodynamic model and to screen reasonable covariates to quantitatively describe the efficacy of poly (ADP-ribose) polymerase inhibitors (PARPis) as maintenance treatment for recurrent ovarian cancer (ROC).Methods: The log normal hazard function model was established by using progression-free survival (PFS) data of 1,169 patients from published randomized trials on FDA-approved PARP inhibitors (olaparib, niraparib, and rucaparib). Monte Carlo simulation was used to compare PFS values in different scenarios, such as monotherapy (administered alone) and combination therapy (PARPis combined with chemo- or target-therapies), different biomarker statuses, and different PARP inhibitors. PFS was also estimated.Results: The study showed that the median PFS was 8.5 months with monotherapy and 16.0 months with combination therapy. The median PFS of patients with the BRCA mutation, BRCA wild-type, and HRD-positivity were 11.0, 7.5, and 9.0 months in monotherapy, respectively, and 23.0, 14.0 and 17.5 months, in combination therapy, respectively. In addition, the median PFS of olaparib, niraparib, and rucaparib monotherapy were about 9.5, 10.5, and 12.0 months, respectively, and about 19.0, 20.0, and 25 months, respectively, in combination therapy. The median PFS values in combination with cediranib, bevacizumab, and chemotherapy were approximately 17.0, 12.5 and 19.5 months, respectively.Conclusion: PARPi combination therapy is more effective as maintenance treatment for ROC than monotherapy, and the efficacy of PARPis in combination with chemotherapy is higher than that of the combination with antiangiogenic drugs. We found that the PFS of BRCA wild-type was similar to that of HRD-positive patients, and there was no significant difference in PFS between olaparib, niraparib, and rucaparib, which provides necessary quantitative information for the clinical practice of PARPis in the treatment of ROC.
format	article
author	Lili Gao Rui Chen Ting Li Lujin Li Qingshan Zheng
author_facet	Lili Gao Rui Chen Ting Li Lujin Li Qingshan Zheng
author_sort	Lili Gao
title	Quantitative Analysis of the Efficacy of PARP Inhibitors as Maintenance Therapy in Recurrent Ovarian Cancer
title_short	Quantitative Analysis of the Efficacy of PARP Inhibitors as Maintenance Therapy in Recurrent Ovarian Cancer
title_full	Quantitative Analysis of the Efficacy of PARP Inhibitors as Maintenance Therapy in Recurrent Ovarian Cancer
title_fullStr	Quantitative Analysis of the Efficacy of PARP Inhibitors as Maintenance Therapy in Recurrent Ovarian Cancer
title_full_unstemmed	Quantitative Analysis of the Efficacy of PARP Inhibitors as Maintenance Therapy in Recurrent Ovarian Cancer
title_sort	quantitative analysis of the efficacy of parp inhibitors as maintenance therapy in recurrent ovarian cancer
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/585acc5210064b1aa454b88a24087b05
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Quantitative Analysis of the Efficacy of PARP Inhibitors as Maintenance Therapy in Recurrent Ovarian Cancer

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