Phase 2 study of carfilzomib for the treatment of patients with advanced neuroendocrine cancers.

382Background: Carfilzomib (CFZ) is an irreversible proteasome inhibitor (PI) that exhibits anti-proliferative and pro-apoptotic activity in solid and hematologic tumor cells in vitro, and is US FDA approved for multiple myeloma. Proteasomes degrade cell cycle inhibitor proteins and inhibition of these proteins offers a novel therapy for the treatment of patients with neuroendocrine tumors (NET). This phase 2 study evaluated the efficacy of CFZ for patients with advance NETs. Methods: Pts with biopsy-proven, advanced, well-to-moderately differentiated NETs, including typical carcinoid and pancreatic islet cell tumors, were treated with CFZ 20 mg/m2 IV Days (D) 1 and 2, then 56 mg/m2 IV D 8, 9, 15, and 16 of Cycle (C) 1, followed by CZF 56 mg/m2 IV D 1, 2, 8, 9, 15, and 16 of C 2 and beyond. Pts continued study treatment (tx) until intolerable toxicity, disease progression, or withdrawal of consent. Restaging occurred every 3 cycles. The primary endpoint was overall response rate (ORR); secondary endpoints...