Etirinotecan Pegol Shows Activity in Recurrent Platinum-Resistant/Refractory Epithelial Ovarian Cancer
Etirinotecan pegol is a topoisomerase-I inhibitor that prolongs systemic exposure to the active metabolite of irinotecan. In a phase II trial reported in Journal of Clinical Oncology, Ignace B. Vergote, MD, PhD, of University Hospital Leuven in Belgium, and colleagues found that the agent produced encouraging responses and progression-free survival in women with platinum-resistant/refractory ovarian carcinoma.
In the study, 71 patients were randomly assigned to receive etirinotecan pegol at 145 mg/m2 every 14 (n = 36) or 21 days (n = 35) until progression or unacceptable adverse events. The primary endpoint was objective response rate by RECIST criteria.
Response Rates
The overall confirmed objective response rate was 20%, including 20% in the every-14-day group and 19% in the every-21-day group. Clinical benefit (objective response or stable disease ≥ 3 months) was observed in 54% of patients in the every-14-day group and 48% in the every-21-day group.
The objective response rate in patients who had received prior pegylated liposomal doxorubicin was similar to that in the overall population. The response rate was 7% in platinum-refractory patients and 24% in platinum-resistant patients. Median response duration was 4.1 months in the every-14-day group vs 4.0 months in the every-21-day group, median progression-free survival was 4.1 vs 5.3 months, and median overall survival was 10.0 vs 11.7 months.
On Gynecologic Cancer Intergroup criteria, the overall response rate was 33%, with one complete response. Of all patients with evaluable levels of CA-125 at baseline, 12% had complete response and 28% had partial response on CA-125 criteria.
Toxicities
Diarrhea, dehydration, nausea, and neutropenia were more common in the every-14-day group. The most common grade 3 to 4 adverse events were dehydration (28% in every-14-day group vs 20% in every-21-day group), diarrhea (31% vs 14%), hypokalemia (25% vs 14%), fatigue (14% vs 23%), and nausea (25% vs 11%).
The investigators concluded: “Both schedules of etirinotecan pegol showed activity in patients with heavily pretreated ovarian cancer, with encouraging [objective response and progression-free survival] rates. The schedule of once every 21 days was better tolerated and had slightly longer [progression-free survival and overall survival] rates. The treatment schedule of etirinotecan pegol 145 mg/m2 once every 21 days was selected for the expanded phase II study and is preferred for future phase III studies.”
The study was supported by Nektar Therapeutics.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
