AEZS-108 (zoptarelin doxorubicin) is a cytotoxic hybrid molecule consisting of doxorubicin covalently coupled with a luteinizing hormone-releasing hormone (LHRH) analogue, which selectively targets doxorubicin to tumor cells expressing LHRH receptors. We report the clinical efficacy of AEZS-108 in a phase II trial in men with metastatic castrate-resistant prostate cancer who had disease progression after taxane-based chemotherapy.
Patients received AEZS-108 210 mg/m(2) intravenously every 3 weeks. The primary end point was clinical benefit defined as nonprogression at 12 weeks with no dose-limiting toxicities (DLTs) or other toxicities requiring termination of treatment. Secondary end points included response rate, pain response, progression-free survival (PFS), and overall survival (OS). Circulating tumor cells (CTCs) were captured and tested for LHRH receptors, as well as for internalization of AEZS-108 using autofluorescence.
Twenty-five patients were enrolled; 20 patients had at least 1 measurable lesion at baseline. Patients received a median of 5 cycles (range, 1-9) and 44% of patients received at least 6 cycles with 2 patients who completed ≥ 8 cycles. Considering clinical benefits, 13 patients (52%) remained progression-free at 12 weeks with no DLT or other toxicities requiring termination of treatment. For clinical response according to Response Evaluation Criteria in Solid Tumors version 1.1 criteria, 1 patient (4%) experienced a confirmed partial response (PR) within 12 weeks, 14 patients (56%) had stable disease (SD), and 8 patients (32%) had disease progression. For maximal prostate-specific antigen (PSA) response, 1 patient (4%) experienced a confirmed PR within 12 weeks, 21 patients (84%) had SD, and 3 patients (12%) had disease progression as denoted by their best PSA response. Pain improved in 13 (59%) patients. The median PFS was 3.8 months (95% confidence interval [CI], 2.1-4.4), and median OS was 6.0 months (95% CI, 4.2-10.1) with a median follow-up of 16.1 months (range, 3.2-36.1). Baseline CTC enumeration was an independent predictor of OS but not PFS.
AEZS-108 showed activity in patients who were pretreated, a subset typically very difficult to treat, and maintained an acceptable safety profile.
Clinical genitourinary cancer. 2017 Jun 08 [Epub ahead of print]
Steven S Yu, Kanthi Athreya, Stephen V Liu, Andrew V Schally, Denice Tsao-Wei, Susan Groshen, David I Quinn, Tanya B Dorff, Shigang Xiong, Jurgen Engel, Jacek Pinski
Division of Oncology, University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA., Division of Oncology, Georgetown University, Lombardi Comprehensive Cancer Center, Washington, DC., Division of Hematology/Oncology, University of Miami, Miller School of Medicine, Miami, FL., Division of Preventive Medicine, University of Southern California, Los Angeles, CA., Aeterna Zentaris, Inc, Charleston, South Carolina., Division of Oncology, University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA. Electronic address: .