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

Lili Gao; Rui Chen; Ting Li; Lujin Li; Qingshan Zheng

doi:10.3389/fphar.2021.771836

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

Front Pharmacol. 2021 Nov 8:12:771836. doi: 10.3389/fphar.2021.771836. eCollection 2021.

Authors

Lili Gao¹, Rui Chen¹, Ting Li¹, Lujin Li¹, Qingshan Zheng¹

Affiliation

¹ Center for Drug Clinical Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Abstract

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.

Keywords: PARP; maintenance treatment; pharmacodynamic model; progress-free survival; recurrent ovarian cancer.