Recent targeted therapies such as poly-ADP ribose polymerase inhibitors (PARPi) and angiogenesis inhibitors (AI) are known to ease burden and recurrence of ovarian cancer. This network meta-analysis conducted an indirect treatment comparison between PARPi, AI and chemotherapeutic agents (CTA) in terms of clinical efficacy and safety as maintenance therapy in ovarian cancer patients irrespective of BRCA status.
We searched relevant sources (PubMed, EMBASE) to identify randomized controlled trials in ovarian cancer patients undergoing maintenance therapy. Studies assessing efficacy and safety of PARPi (n = 4), AIs (n = 12), CTA (n = 8) with placebo were analyzed. Primary outcome included progression free survival (PFS), safety and tolerability were secondary outcomes. A network meta-analysis to compare 3 drug classes was performed using statistical software R.
PARPi [Hazard Ratio (HR) =0.64; 95% Credible Intervals (CrI) =0.55-0.73] and AI (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, Table). PARPi showed significant improvement in PFS compared to AI (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 PARPi [Incidence Rate Ratio (IRR) =1.64; CrI=0.84-3.19, IRR=0.73, 95% CrI=0.50-1.06 respectively] compared to AI, but not significant.Table: 976P
Comparison of PFS data across different therapies
|AI||-||1.14 (0.98, 1.35)||0.73 (0.63, 0.86)||1.15 (1.07, 1.24)|
|CTA||0.87 (0.74, 1.02)||-||0.64 (0.52, 0.78)||1.00 (0.87, 1.16)|
|PARPi||1.37 (1.16, 1.6)||1.57 (1.28, 1.92)||-||1.57 (1.36, 1.81)|
|Placebo||0.87 (0.81, 0.93)||1.00 (0.86, 1.15)||0.64 (0.55, 0.73)||-|
AI angiogenesis inhibitors; CTA chemotherapeutic agents; PARPi poly ADP ribose polymerase inhibitors.
PARPi as maintenance treatment improved PFS in ovarian cancer and was relatively safer in terms of AEs caused implications when compared to other therapies. This network meta-analysis provides valuable evidence and significant insights in treatment of ovarian cancer.
Clinical trial identification
Legal entity responsible for the study
Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou.
All authors have declared no conflicts of interest.