Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Feb 22:10:573801.
doi: 10.3389/fonc.2020.573801. eCollection 2020.

Comparative Efficacy and Safety of PARP Inhibitors as Maintenance Therapy in Platinum Sensitive Recurrent Ovarian Cancer: A Network Meta-Analysis

Yangchun Xu  1 , Lei Ding  2 , Yuan Tian  3 , Miaomiao Bi  4 , Ning Han  2 , Ling Wang  5
Affiliations

Comparative Efficacy and Safety of PARP Inhibitors as Maintenance Therapy in Platinum Sensitive Recurrent Ovarian Cancer: A Network Meta-Analysis

Yangchun Xu et al. Front Oncol. .

Abstract

This meta-analysis investigated the comparative efficacy and safety of PARP inhibitor monotherapy as maintenance treatment in platinum sensitive recurrent ovarian cancer (ROC). Electronic databases were systematically searched for relevant RCTs. The primary endpoint was PFS. The results were stratified based on three categories: BRCA mutated patients, HRD patients, and overall population. The secondary outcome were discontinuations due to adverse events and grade 3 or 4 adverse events in maintenance phase. Five eligible RCTs were included in the network meta-analysis. For patients with BRCA mutated ovarian cancer, olaparib-throughout (HR = 0.21 with 95% CrI: 0.081-0.55), rucaparib (HR = 0.23 with 95% CrI: 0.16-0.34), olaparib (HR = 0.27 with 95% CrI: 0.20-0.35), and niraparib (HR = 0.26 with 95% CrI: 0.17-0.41) were all highly effective in comparison with placebo at improving PFS. For HRD patients, both rucaparib (HR = 0.32 with 95% CrI: 0.24-0.42) and niraparib (HR = 0.38 with 95% CrI: 0.24-0.60) were all highly effective in comparison with placebo at improving PFS. For the overall population, olaparib-throughout (HR = 0.51 with 95% CrI: 0.34-0.76), rucaparib (HR = 0.37 with 95% CrI: 0.30-0.45), olaparib (HR = 0.35 with 95% CrI: 0.25-0.49), and niraparib (HR = 0.38 with 95% CrI: 0.30-0.48) were all highly effective in comparison with placebo at improving PFS. Regarding grade 3 or 4 adverse events, the incidence of grade 3 or 4 toxicity reactions to rucaparib and niraparib were significantly higher than in the olaparib group. In terms of discontinuations due to adverse events, the treatment discontinuations were not significantly different between the three drugs. In summary, all the included maintenance treatment regimens are effective regardless of BRCA mutational status, and no statistically significant differences between rucaparib, niraparib and Olaparib in terms of PFS. In terms of safety profile, the three drugs present manageable adverse events. Clinicians should consider potential adverse events related to each of these interventions in clinical practice, and the adverse events are generally manageable.

Keywords: PARP inhibitor; network meta-analysis; ovarian cancer; platinum; progress-free survival.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Study Flow Diagram.
Figure 2
Figure 2
Network of the comparisons for the network meta-analysis. (A) PFS in BRCA mutated patients; (B) PFS in HRD positive patients; (C) PFS in overall population; (D) Network meta‐analysis of discontinuations due to adverse events; (E) Network meta‐analysis of adverse events in maintenance phase. Each circular node represents a type of treatment. The circle size is proportional to the total number of studies (under the drug name). The width of lines is proportional to the number of studies performing head-to-head comparisons in the same study.
Figure 3
Figure 3
Network meta‐analysis of PFS in BRCA mutated patients.
Figure 4
Figure 4
Network meta‐analysis of PFS in HRD positive patients.
Figure 5
Figure 5
Network meta‐analysis of PFS in overall population.
Figure 6
Figure 6
Network meta‐analysis of discontinuations due to adverse events.
Figure 7
Figure 7
Network meta‐analysis of adverse events in maintenance phase.
See this image and copyright information in PMC

References

    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin (2019) 69(1):7–34. 10.3322/caac.21551 - DOI - PubMed
    1. Moore K, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, et al. . Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med (2018) 379(26):2495–505. 10.1056/NEJMoa1810858 - DOI - PubMed
    1. Shao F, Liu J, Duan Y, Li L, Liu L, Zhang C, et al. . Efficacy and safety of PARP inhibitors as the maintenance therapy in ovarian cancer: a meta-analysis of nine randomized controlled trials. Biosci Rep (2020) 40(3):BSR20192226. 10.1042/BSR20192226 - DOI - PMC - PubMed
    1. Ibrahim EM, Refae AA, Bayer AM, Sagr ER. Poly(ADP-ribose) polymerase inhibitors as maintenance treatment in patients with newly diagnosed advanced ovarian cancer: a meta-analysis. Future Oncol (2020) 16(10):585–96. 10.2217/fon-2020-0057 - DOI - PubMed
    1. Tomao F, Bardhi E, Di Pinto A, Sassu CM, Biagioli E, Petrella MC, et al. . Parp inhibitors as maintenance treatment in platinum sensitive recurrent ovarian cancer: An updated meta-analysis of randomized clinical trials according to BRCA mutational status. Cancer Treat Rev (2019) 80:101909. 10.1016/j.ctrv.2019.101909 - DOI - PubMed

Publication types

LinkOut - more resources