Trabectedin plus pegylated liposomal doxorubicin (PLD) versus PLD in recurrent ovarian cancer: Overall survival analysis

• Published in: European journal of cancer (1990) Vol. 48; no. 15; pp. 2361 - 2368
• Main Authors: Monk, Bradley J., Herzog, Thomas J., Kaye, Stanley B., Krasner, Carolyn N., Vermorken, Jan B., Muggia, Franco M., Pujade-Lauraine, Eric, Park, Youn C., Parekh, Trilok V., Poveda, Andres M.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.10.2012; Elsevier
• Subjects: Aged; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Carcinoma, Ovarian Epithelial; Dioxoles - administration & dosage; Disease-Free Survival; Doxorubicin - administration & dosage; Doxorubicin - analogs & derivatives; Doxorubicin - therapeutic use; Female; Hematology, Oncology and Palliative Medicine; Humans; Medical sciences; Middle Aged; Neoplasm Recurrence, Local; Neoplasms, Glandular and Epithelial - drug therapy; Neoplasms, Glandular and Epithelial - pathology; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - pathology; Pegylated liposomal doxorubicin; Pharmacology. Drug treatments; Polyethylene Glycols - administration & dosage; Polyethylene Glycols - therapeutic use; Recurrent ovarian cancer; Survival Analysis; Tetrahydroisoquinolines - administration & dosage; Trabectedin; Tumors; Trabectedin; Pegylated liposomal doxorubicin; Recurrent ovarian cancer; Antineoplastic agent; DNA topoisomerase (ATP-hydrolysing); Relapse; Enzyme; Ovary cancer; Enzyme inhibitor; Liposome; Topoisomerase II inhibitor; Malignant tumor; Doxorubicin; Survival; Female genital diseases; Ovarian diseases; Isomerases; Cancerology; Anthracyclins; Pegylated form; Comparative study; Cancer
• ISSN: 0959-8049; 1879-0852; 1879-0852
• DOI: 10.1016/j.ejca.2012.04.001

Trabectedin in combination with pegylated liposomal doxorubicin (PLD) improves progression-free survival (PFS) compared to PLD alone in recurrent ovarian cancer (J Clin Oncol 2010;28:3107–14). Women, stratified by performance status (0–1 versus 2) and platinum sensitivity (platinum-free interval [PFI]<6 versus ⩾6months), were randomly assigned to receive PLD 30mg/m2 IV followed by a 3-h infusion of trabectedin 1.1mg/m2 every 3weeks or PLD 50mg/m2 every 4weeks. The study was powered to show a 33% increase in overall survival (OS) after 520 deaths had occurred. After a median follow-up of 47.4months, there were 522 deaths among 672 subjects. The median OS for trabectedin+PLD and PLD arms was 22.2 and 18.9months, respectively (hazard ratio [HR]=0.86; 95% confidence interval [CI]: 0.72–1.02; p=0.0835). An unexpected but significant imbalance in the PFI favouring the PLD arm (mean PFI: PLD=13.3months, trabectedin+PLD=10.6months) was identified. On the basis of this finding, an unplanned hypothesis generating analysis adjusting for the PFI imbalance and other prognostic factors suggested an improvement in OS associated with the trabectedin+PLD arm (HR=0.82; 95%CI: 0.69–0.98; p=0.0285). In another unplanned exploratory analysis, the subset of patients with a PFI of 6–12months had the largest difference in OS (HR=0.64; 95%CI: 0.47–0.86; p=0.0027). The final OS analysis did not meet the protocol-defined criterion for statistical significance. Despite stratification on platinum sensitivity, there was an imbalance in mean platinum free interval that had an effect on OS.