Next Article in Journal
The FGF/FGFR System in Breast Cancer: Oncogenic Features and Therapeutic Perspectives
Previous Article in Journal
Immune Checkpoint Inhibitors in Hepatocellular Carcinoma: Current Status and Novel Perspectives
Open AccessArticle

Comparison of Poly (ADP-ribose) Polymerase Inhibitors (PARPis) as Maintenance Therapy for Platinum-Sensitive Ovarian Cancer: Systematic Review and Network Meta-Analysis

1
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
2
Internal Medicine II, Cardiology, Medical University Vienna, General Hospital Vienna, AKH, 1090 Vienna, Austria
3
Davidoff Center, Rabin Medical Center, Petah Tikva 4941492, Israel
*
Author to whom correspondence should be addressed.
Equal contributors.
Cancers 2020, 12(10), 3026; https://doi.org/10.3390/cancers12103026
Received: 27 September 2020 / Revised: 12 October 2020 / Accepted: 16 October 2020 / Published: 18 October 2020
(This article belongs to the Section Systematic Review or Meta-Analysis in Cancer Research)
Poly (ADP-ribose) polymerase inhibitors (PARPis; inhibitors of a family of enzymes that are primary involved in DNA repair) are considered to be the drug of choice in maintenance therapy for platinum-sensitive ovarian cancer. However, despite the FDA approval of three such agents and their availability in clinical practice, thus far, no clinical trial investigated them in a head-to-head direct comparison. In this study, we used a statistical approach that allows comparing direct and indirect evidence (network meta-analysis) in order to compare the three FDA-approved PARPis (olaparib, niraparib and rucaparib). To this end, we used data from six randomized control trials involving a total of 2270 ovarian cancer patients. Interestingly, we found no significant differences in clinical outcomes (overall survival and progression-free survival) between the three agents. However, niraparib was found to be associated with higher risk of certain adverse events (thrombocytopenia, neutropenia, constipation, and headaches) compared to the other two PARPis.
Background: Three PARPis (olaparib, niraparib and rucaparib) are currently FDA-approved as maintenance therapy in newly diagnosed and recurrent ovarian cancer. However, thus far, no trial has compared the three approved PARPis in the overall population, in patients with BRCA mutations, or in those with wild-type BRCA. Methods: A frequentist network meta-analysis was used for indirect comparisons between the different PARPis with respect to progression free survival (PFS), overall survival (OS), and adverse events. Results: Overall, six randomized clinical trials involving 2,770 patients, were included in the analysis. Results from the indirect comparisons revealed no statistically significant differences between the three PARPis with respect to PFS or OS in the entire population and in patients with mutated and wild-type BRCA, separately. Niraparib showed a statistically significant increased risk for grade 3 and 4 thrombocytopenia (risk-difference [RD] from placebo: 0.3; 95% confidence interval [CI], 0.27‒0.34) and any grade neutropenia (RD from placebo: 0.22; 95% CI, 0.18‒0.25) as compared with the other PARPis. Conclusion: No statistically significant difference was found between the three PARPis with respect to PFS or OS (overall and in subpopulations by BRCA status). There is, however, a statistical difference in toxicity as niraparib is associated with a greater risk for thrombocytopenia and neutropenia. View Full-Text
Keywords: adverse event; network meta-analysis; ovarian cancer; overall survival; poly (ADP-ribose) polymerase inhibitor; platinum-sensitive; progression-free survival adverse event; network meta-analysis; ovarian cancer; overall survival; poly (ADP-ribose) polymerase inhibitor; platinum-sensitive; progression-free survival
Show Figures

Figure 1

MDPI and ACS Style

Stemmer, A.; Shafran, I.; Stemmer, S.M.; Tsoref, D. Comparison of Poly (ADP-ribose) Polymerase Inhibitors (PARPis) as Maintenance Therapy for Platinum-Sensitive Ovarian Cancer: Systematic Review and Network Meta-Analysis. Cancers 2020, 12, 3026.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop