Molecular targeted therapy in combination with chemotherapy for the treatment of platinum-resistant/refractory ovarian cancer (PROC): a systematic review and network meta-analysis

Although single-agent chemotherapy is the most common approach for treating platinum-resistant or refractory ovarian cancer (PROC), there is growing evidence that combining molecular targeted agents with chemotherapy is beneficial, especially for certain patient groups. However, the most effective combination regimen remains elusive.
This Bayesian network meta-analysis (NMA) aims to identify the best combination therapy for PROC.
Relevant studies were searched in PubMed, EMBASE, Web of Science and the Cochrane Central Register of Controlled Trials from their inception until October 2024. The primary outcomes were overall survival (OS), progression-free survival (PFS) and adverse events (AEs). Statistical analyses were performed using the GEMTC package (1.0-2) and R 4.2.0. This review was registered in PROSPERO (CRD42023428414).
Our analysis of 22 randomized controlled trials (RCTs) (n = 3408) demonstrated that chemotherapy combinations with bevacizumab (hazard ratio (HR) = 0.52–0.65), sorafenib (HR = 0.65, 95% confidence interval (CI): 0.45–0.93) or adavosertib (HR = 0.56, 95%CI: 0.35–0.90) significantly improved OS and PFS versus chemotherapy alone. Notably, adavosertib + gemcitabine was associated with an increased risk of grade 3–4 AEs (relative risk (RR) = 1.8, 95%CI: 1.3–2.7), but these were generally manageable.
Bevacizumab-based combinations demonstrate consistent benefits across multiple regimens for PROC. Paclitaxel + bevacizumab emerges as the optimal balance of efficacy and safety. Topotecan + sorafenib could be an alternative for patients who are ineligible for anti-angiogenic therapy.

Targeted therapy + chemotherapy may be superior to standalone chemotherapy in PROC.
Gemcitabine + bevacizumab can improve PFS of PROC patients.
While effective, adavosertib + gemcitabine is associated with increased toxicity, requiring careful patient selection.

Targeted therapy + chemotherapy may be superior to standalone chemotherapy in PROC.
Gemcitabine + bevacizumab can improve PFS of PROC patients.
While effective, adavosertib + gemcitabine is associated with increased toxicity, requiring careful patient selection.