Randomized phase II parallel evaluation of OSI-211 (liposomal lurtotecan) and topotecan in women with relapsed epithelial ovarian cancer (EOC)

Abstract

5017 Background: OSI-211 is a liposomal formulation of lurtotecan, a topoisomerase-I inhibitor. In a previous randomised dose ranging/feasibility trial a day 1, 2, and 3 q 3/52 regimen was chosen for further evaluation. We present here a randomized phase II, parallel evaluation of OSI-211 and topotecan (TOP) to better estimate the drug’s efficacy and safety using this schedule, standardised for occult pt. selection factors, and to guide a decision whether to proceed with an appropriately powered, randomised phase III trial. Methods: Entry criteria comprised pts. with relapsed EOC, treated with 1 or 2 prior regimens (at least 1 platinum containing) & measurable disease. Pts were randomized to receive OSI-211 1.8 mg/m2 daily x 3 or TOP 1.5 mg/m2 daily x 5, q 3/52 & stratified according to number of prior regimens (1 or 2) and time from last chemotherapy (< 6mos vs. ≥ 6mos). Objective response rate (ORR) was measured using RECIST; toxicity with NCI CTC v2.0. Results: 82 pts of median age 59 yrs (34–82) were randomized, 40 to OSI -211 and 42 to TOP (1 never treated). Treatment groups were well balanced with for interval from last chemotherapy, number of prior regimens, histology and PS. A total of 200 cycles of OSI-211 (range: 1–18) and 176 cycles of TOP (range: 1–8) were administered, with a median of 5 for each arm. Toxicity was comparable for both (G3/4: OSI-211 43% TOP 41%) with asthenia (70% vs. 63%), nausea (50% vs. 51%), vomiting (30% vs. 39%) and diarrhea (20 vs.20%) being the most frequently reported non-hematological toxicity for OSI-211 and TOP. Grade 3/4 febrile neutropenia, G3 thrombocytopenia and sepsis were reported in 3% vs. 12%, 10% vs. 0% and 5% each, in the OSI-211 and TOP pts respectively. The ORR for OSI-211 was 13% (95%CI: 4–27; 5 PR) and 12% for TOP (CI: 4–26; 1CR, 4PR), predominantly in sensitive pts (last chemotherapy ≥ 6mos), with a disease control rate (ORR+SD) of 70% and 71% for OSI-211 and TOP respectively. Median TTP & survival for OSI-211 & TOP was 26 vs. 29 wks & 12 vs. 11mos. Conclusions: OSI-211 is an active agent in relapsed EOC with ostensibly similar efficacy and toxicity to the standard regimen of TOP in this non-comparative study, but with the benefit of a reduced number of dosing days. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration OSI OSI