Comparison of poly (ADP-ribose) polymerase inhibitors (PARPis) as maintenance therapy for newly-diagnosed and platinum-sensitive recurrent ovarian cancer with BRCA mutational status: a systematic review and network meta-analysis

ABSTRACT

Background

Poly(adenosine diphosphate [ADP]–ribose) polymerase inhibitors (PARPi) treatment for ovarian cancer (OC) are ever-changing. This study aimed to compare the efficacy and overall safety of available PARPi as maintenance therapy for BRCA mutation status in patients with newly diagnosed and platinum-sensitive recurrent (PSR) OC patients.

Research design and methods

Relevant RCTs were systematically retrieved from PubMed and Embase until 31 May 2022. Progression-free survival (PFS) and overall survival (OS) based on BRCA mutation status and adverse events (AEs) regardless of mutation were efficacy and safety endpoints.

Results

In newly diagnosed BRCAm-OC patients, olaparib (HR: 0.33; 95% confidence interval [CI]: 0.25, 0.43) and other PARPis [niraparib (HR: 0.40; 95% CI: 0.29, 0.55), rucaparib (HR: 0.40; 95% CI: 0.21, 0.76) and veliparib (HR: 0.44; 95% CI: 0.28, 0.69)] had a statistically significant effect on PFS versus placebo. In BRCAm-PSROC patients, Olaparib exhibited significant benefit (HR: 0.69; 95% CI: 0.54, 0.88) for OS compared to other PARPis. In BRCAwt-PSR OC patients, Olaparib showed a favorable OS benefit than other PARPis (HR: 0.84; 95% CI: 0.57,1.22). Overall, safety profile of all PARPis was acceptable.

Conclusion

All PARPis showed significant benefit, with olaparib showing greater benefit in newly diagnosed and PSR OC women.

Registration

CRD42021288932

KEYWORDS:

• Network meta-analysis
• ovarian cancer
• overall survival
• poly(ADP-ribose) polymerase inhibitor
• platinum-sensitive recurrent ovarian cancer
• progression-free survival

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or mending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contribution statement

SZ and YJ contributed to study concept and design. CL and LY were involved in acquisition of data. SZ and LY analyzed and interpreted the data. YJ and CL contributed to drafting of the manuscript. SZ and CL were involved in critical revision of the manuscript for important intellectual content. YJ and LY helped in administrative, technical, or material support. SZ and LY were involved in study supervision. All authors have made a significant contribution to this study and have approved the final manuscript.

Data availability statement

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

Additional information

Funding

This paper was not funded.