Combinational use of trabectedin and pegylated liposomal doxorubicin for recurrent ovarian cancer: a meta-analysis of phase III randomized controlled trials

Chao Li; Siyi Qiao; Min Kang; Xiaofeng Gao; Zhiru Li

Combinational use of trabectedin and pegylated liposomal doxorubicin for recurrent ovarian cancer: a meta-analysis of phase III randomized controlled trials

Am J Transl Res. 2023 Dec 15;15(12):6675-6689. eCollection 2023.

Authors

Chao Li¹, Siyi Qiao², Min Kang³, Xiaofeng Gao¹, Zhiru Li⁴

Affiliations

¹ Department of Obstetrics and Gynecology, Sichuan Provincial People's Hospital·Qionglai Medical Center Hospital Chengdu, Sichuan, The People's Republic of China.
² He University Shenyang, Liaoning, The People's Republic of China.
³ Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University Nanning, Guangxi, The People's Republic of China.
⁴ Department of Oncology, Sichuan Provincial People's Hospital·Qionglai Medical Center Hospital Chengdu, Sichuan, The People's Republic of China.

PMID: 38186978
PMCID: PMC10767539

Abstract

Background: In recent years, pegylated liposomal doxorubicin (PLD) has been widely used to improve the survival of patients with ovarian cancer; however, it is unclear whether the combinational use of PLD with other drugs is more effective. Therefore, this meta-analysis aimed to confirm the efficacy and safety of trabectedin, combined with PLD, in the treatment of recurrent ovarian cancer.

Methods: Data corresponding to all eligible clinical trials as of May 15, 2022, was retrieved using several electronic retrieval databases including PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), ClinicalTrials.gov, Excerpta Medica Database (EMBASE) and Cochrane Library clinical controlled trials (CENTRAL). Comprehensive hazard ratios (HRs), risk ratios (RRs), and 95% confidence intervals (CIs) were calculated using the Review Manager software 5.4 (RevMan 5.4).

Results: From two phase III randomized controlled trials, 1248 patients with recurrent ovarian cancer were included in this meta-analysis. Results of meta-analysis revealed that trabectedin, combined with PLD chemotherapy, significantly improved overall survival (OS) in patients with BReast CAncer gene (BRCA)-associated recurrence (HR, 0.49; 95% CI, [0.33-0.73]; P = 0.0004) and platinum-sensitive recurrence whose platinum-free interval (PFI) was 6-12 months (HR, 0.66; 95% CI, [0.52-0.84]; P = 0.0005). In addition, compared with PLD alone, combination therapy significantly improved the progression-free survival (PFS) in patients with recurrent ovarian cancer (HR, 0.86; 95% CI, [0.74-0.99]; P = 0.03). Combination therapy also significantly improved PFS in patients with BRCA-associated recurrence (HR, 0.58; 95% CI, [0.40-0.58]; P = 0.004), and platinum-sensitive recurrence (HR, 0.73; 95% CI, [0.56-0.95]; P = 0.02). Trabectedin combined with PLD was more prone to grade 3-4 toxic side effects than PLD alone (P < 0.05); however, fatal adverse events related to non-toxic side effects occurred.

Conclusion: Trabectedin combined with PLD significantly improves OS and PFS in patients with BRCA-associated and platinum-sensitive recurrent ovarian cancers. The potential use of trabectedin combined with PLD should be selected according to the PFI and BRCA mutation status of patients.

Keywords: Trabectedin; chemotherapy; meta-analysis; pegylated liposomal doxorubicin; relapsed ovarian cancer.

Publication types

Review