Efficacy, Safety, and Prognosis of Current Phase III Chemotherapy for Platinum-Resistant Ovarian Cancer: A Systematic Review

Abstract

Platinum-resistant ovarian cancer is associated with poor prognosis, and chemotherapy remains widely used despite modest efficacy. This systematic review evaluated the efficacy and safety of chemotherapy in platinum-resistant ovarian cancer using phase III randomized trials. The review followed PRISMA 2020 guidelines and was registered in PROSPERO (CRD42024593673). PubMed, Embase, ScienceDirect, and the Cochrane Central Register of Controlled Trials were searched for phase III randomized trials investigating chemotherapy in recurrent platinum-resistant ovarian cancer. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Three phase III randomized trials met the inclusion criteria. Median progression-free survival ranged from approximately 3 to 8 months, while no consistent overall survival benefit was observed across chemotherapy strategies. Combination regimens increased objective response rates. Dose modification and alternative scheduling maintained comparable efficacy while improving tolerability, whereas novel cytotoxic agents did not demonstrate superiority over standard chemotherapy. All included studies raised some risk-of-bias concerns, primarily because of open-label designs. Overall, the evidence indicates that cytotoxic chemotherapy offers modest, short-lived clinical benefit, with limited impact on overall survival. Dose-optimized pegylated liposomal doxorubicin (40 mg/m²) appears practical, as it preserves efficacy while improving tolerability. Lurbinectedin has not demonstrated improved outcomes in this patient population. Although trabectedin plus pegylated liposomal doxorubicin may improve response rates and prolong progression-free survival, additional toxicity and the absence of an overall survival benefit restrict its use to selected patients. Therefore, chemotherapy should primarily support symptom control and short-term disease stabilization. Future improvements will likely depend on biomarker-guided targeted strategies.