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Comparison of PARPis with Angiogenesis Inhibitors and Chemotherapy for Maintenance in Ovarian Cancer: A Network Meta-Analysis

Abstract

Introduction

Seventy-five percent of ovarian cancer would relapse within 18–28 months after platinum-base chemotherapy. Evidence suggests that maintenance chemotherapy is effective in prolonging remission. Recent target therapies such as poly(ADP-ribose) polymerase inhibitors (PARPis) and angiogenesis inhibitors (AIs) are known to ease burden and recurrence of ovarian cancer. There is limited data for head-to-head comparison of PARPis, AIs, and chemotherapeutic agents (CTAs) as maintenance treatment. This network meta-analysis thus assessed the effectiveness and toxicity of these three maintenance therapies in patients with ovarian cancer.

Methods

We searched relevant sources (PubMed, EMBASE) to identify randomized controlled trials assessing efficacy and safety of maintenance therapy in patients with ovarian cancer. Primary outcome was progression-free survival (PFS) as assessed by blinded review; safety and tolerability were secondary outcomes. A network meta-analysis to compare three drug classes was performed using statistical software R.

Results

We included 24 trials (11,366 patients) assessing efficacy and safety of PARPis (n = 4), AIs (n = 12), and CTAs (n = 8). PARPis [hazard ratio (HR) 0.64; 95% credible intervals (CrI) 0.55–0.73] and AIs (HR 0.87; 95% CrI 0.81–0.93) showed significant improvement in PFS compared to placebo but not CTA (HR 1.00; 95% CrI 0.86–1.15). PARPis showed significant improvement in PFS compared to AIs (HR 0.73; 95% CrI 0.63–0.86) and CTA (HR 0.64; 95% CrI 0.52–0.78). Adverse events (AEs) leading to treatment discontinuation and dose reduction were lower in PARPis [incidence rate ratio (IRR) 0.60; CrI 0.31–1.18 and IRR 0.73, 95% CrI 0.50–1.06, respectively] compared to AIs, but the differences were not significant.

Conclusion

PARPi as maintenance treatment improved PFS in ovarian cancer and was relatively safer in terms of implications caused by AEs when compared to AIs. This network meta-analysis provides valuable evidence and significant insights into treatment of ovarian cancer.

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Acknowledgements

Funding

No funding or sponsorship was received for this study or publication of this article. The Rapid Service Fee was funded by the authors.

Medical Writing Assistance

Medical writing support was provided by Dr Anuradha Nalli and Dr Amit Bhat of Indegene and funded by AstraZeneca China Investment Co., Ltd.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Disclosures

Yanling Feng, He Huang, Ting Wan, Chuyao Zhang, Chongjie Tong, and Jihong Liu have nothing to disclose.

Compliance with Ethics Guidelines

This article is based on previously conducted studies and does not contain any experiments with human participants or animals performed by any of the authors.

Data Availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Correspondence to Jihong Liu.

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Feng, Y., Huang, H., Wan, T. et al. Comparison of PARPis with Angiogenesis Inhibitors and Chemotherapy for Maintenance in Ovarian Cancer: A Network Meta-Analysis. Adv Ther 36, 3368–3380 (2019). https://doi.org/10.1007/s12325-019-01106-1

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Keywords

  • Angiogenesis inhibitors
  • Chemotherapy
  • Maintenance therapy
  • Ovarian cancer
  • PARP inhibitors