Weekly versus tri‐weekly paclitaxel with carboplatin for first‐line treatment in women with epithelial ovarian cancer

Background Epithelial ovarian cancer is the sixth most common cancer worldwide: 295,414 new cases were diagnosed in 2018, with 184,799 deaths. The lack of an effective screening strategy has led to the majority of women being diagnosed at an advanced stage. For these women, intravenous carboplatin combined with paclitaxel for six cycles is widely accepted as the standard first‐line treatment for epithelial ovarian cancer, in combination with debulking surgery. However, there is conflicting evidence regarding the optimal dosing schedule of paclitaxel when combined with carboplatin in this setting. Objectives To compare the efficacy and tolerability of intravenous weekly paclitaxel with that of tri‐weekly paclitaxel, in combination with intravenous carboplatin, as first‐line treatment for epithelial ovarian cancer (defined as epithelial ovarian, primary peritoneal and fallopian tube cancer). Search methods We searched CENTRAL, MEDLINE, and Embase databases for relevant studies up to 15 November 2021, using keywords and MeSH terms. We additionally handsearched conference libraries, online clinical trial databases and screened through lists of retrieved references. Selection criteria We Included randomised controlled trials (RCTs) comparing weekly paclitaxel in combination with carboplatin versus tri‐weekly paclitaxel in combination with carboplatin, for treatment of newly‐diagnosed epithelial ovarian cancer. Data collection and analysis We used the hazard ratio (HR) to estimate the primary efficacy outcomes progression‐free (PFS) and overall survival (OS). We used the risk ratio (RR) to estimate the primary toxicity outcome of severe neutropenia and secondary outcomes of quality of life (QoL) and treatment‐related adverse events. Two review authors independently selected studies, extracted data, and assessed risk of bias, using standard Cochrane methodological procedures. We included individual participant data (IPD) from one of the included studies, ICON‐8, provided by the study team. We analysed data using a random‐effects model in Review Manager 5.4 software. Additionally, we reconstructed IPD for PFS and OS data from published Kaplan‐Meier curves from all studies and subsequently pooled these to analyse the two primary efficacy outcomes. Main results From 2469 records, we identified four eligible RCTs with data for 3699 participants. All eligible studies were included in the main meta‐analysis and reported on PFS and OS. There was likely a slight improvem