Phase II trial of carfilzomib for metastatic castration-resistant prostate cancer (mCRPC) following androgen pathway inhibitors.

Abstract

224 Background: mCRPC is an incurable disease with suboptimal outcomes following prior therapy. Bortezomib, a proteasome inhibitor, has exhibited activity in a subset of patients. Carfilzomib is a second-generation selective and irreversible proteasome inhibitor and is approved for refractory myeloma. Methods: A non-randomized phase II trial (NCT02047253) was designed to evaluate carfilzomib for mCRPC following abiraterone acetate (AA) and/or enzalutamide (enza); prior docetaxel (D) was allowed. A 6-month progression-free survival (PFS) rate ≥30% defined by Prostate Cancer Working Group (PCWG) guidelines was considered important, while PFS < 10% was not. History and physical exam, and prostate specific antigen (PSA) was performed every 4 weeks. Circulating tumor cells (CTCs) were measured at baseline and 12 weeks later. Radiographic evaluation was performed every 12 weeks. Carfilzomib was administered on days 1,2,8,9,15,16 every 28 days. The starting dose was 20 mg/m2 during the first week followed by dose escalation to 56 mg/m2 if no serious toxicities occurred. Daily oral acyclovir was administered for herpes zoster prophylaxis. Therapy continue until PCWG or symptomatic progression or severe toxicities. Results: Twenty-eight patients were recruited and prior AA, enza or D had been received by 21 pts each and 20 pts received > 1 of these agents. The median age was 70 (range 55-88). One patient attained 6-month PFS; 2 other patients progressed at 6 months. Minor PSA declines and CTC declines were observed in 3 patients each, and one patient exhibited both PSA and CTC declines. The major toxicities of any grade were: anemia (n = 13, 46%), Fatigue (n = 7, 25%), and Constipation (n = 5, 18%), with anorexia, cough, fever, headache and thrombocytopenia in 4 patients each (14%). The major toxicities of grade ≥3 in > 1 patient were: anemia (n = 3, 11%) and hypertension (n = 2, 7%). Conclusions: Carfilzomib is not active as salvage therapy following AA and/or enza in unselected patients with mCRPC. Minor and transient activity may be present in a small subset of patients. Clinical trial information: NCT02047253.