A phase III trial of cisplatin plus topotecan followed by paclitaxel plus carboplatin versus standard carboplatin plus paclitaxel as first-line chemotherapy in women with newly diagnosed advanced epithelial ovarian cancer (EOC) (OV.16). A Gynecologic Cancer Intergroup Study of the NCIC CTG, EORTC GCG, and GEICO

Abstract

LBA5505 Background: Topotecan was evaluated in a novel combination regimen in comparison to standard therapy in front-line EOC. Methods: Women with newly diagnosed EOC stages IIB-IV, ECOG PS 0–1, age ≤ 75, and were randomized to one of two q 21 day regimens. Arm 1 cycles 1 to 4: cisplatin 50 mg/m2 d1 plus topotecan 0.75 mg/m2 d1–5 IV; cycles 5 to 8: paclitaxel 175 mg/m2 over 3 hrs d1 followed by carboplatin AUC5 day 1. Arm 2 paclitaxel plus carboplatin as in Arm 1 for 8 cycles. Patients (pts) were stratified for type of primary surgery/residual disease, centre, and age (< 65 vs. > 65 yrs). The primary endpoint was progression free survival (PFS). Progression was defined as the earlier of objective or CA125 progression (GCIG definition) or death. Secondary endpoints were response (in pts with measurable disease), CA125 normalization at 3 mo, overall survival, toxicity and Quality of Life. The sample size required 800 pts and 631 progression events to demonstrate an increase in PFS from 16 to 20 months with a power of 80% and alpha (2-sided) <0.05. Results: 819 pts (409 Arm 1, 410 Arm 2) were entered from Aug 2001 to June 2005. All randomized patients were included in the analysis. 650 pts have had a progression event and 406 have died. Pt characteristics were well balanced. Median age was 57 yrs (range: 28–78); 80% had debulking surgery: of these 55% had < 1 cm residual disease; 8.5% pts were stage II, 66% stage III, 25.5% stage IV. Arm 1 vs Arm 2 pts had more hematological toxicity (gr 3/4 febrile neutropenia 9.9% vs. 2.7%) and hospitalizations (11.3% cycles vs. 7.1% cycles). Conclusions: Topotecan/cisplatin followed by carboplatin/paclitaxel was more toxic and did not show any evidence of improved efficacy compared to standard therapy. Carboplatin plus paclitaxel remains the standard of care for advanced EOC. * stratified log rank; ** stratified Cochran-Mantel-Haenszel No. Pts Arm 1 Arm 2 Hazard Ratio Odds Ratio p value PFS median (mo) 819 14.6 16.2 1.10 (0.94-1.28) 0.25* CR + PR (%) 389 67.9 77.2 0.63 0.04** CA125 normal < 3 mo (%) 819 57.5 66.3 0.63 0.006** Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline