Safety and Efficacy of BIND-014, a Docetaxel Nanoparticle Targeting Prostate-Specific Membrane Antigen for Patients With Metastatic Castration-Resistant Prostate Cancer

作者：Karen A. Autio, Robert Dreicer, Justine Anderson, Jorge A. García, Ajjai Alva, Lowell L. Hart, Matthew I. Milowsky, Edwin M. Posadas, Charles J. Ryan, Ryon P. Graf, Ryan Dittamore, Nicole A. Schreiber, Jason M. Summa, Hagop Youssoufian, Michael J. Morris, Howard I. Scher · 发表于：JAMA Oncology · 年份：2018 · DOI：10.1001/jamaoncol.2018.2168 · 被引用次数：256 · 研究领域：Prostate Cancer Treatment and Research、Prostate Cancer Diagnosis and Treatment、Immunotherapy and Immune Responses

Importance: Preferential delivery of docetaxel to tumors by prostate-specific membrane antigen (PSMA)-targeted nanoparticles is clinically effective, and the selective reduction of PSMA-positive circulating tumor cells (CTCs) after treatment has implications for patient selection and disease monitoring. Objective: To determine the safety and efficacy of BIND-014, a PSMA-directed docetaxel-containing nanoparticle, in patients with metastatic castration-resistant prostate cancer (mCRPC). Design, Setting, and Participants: A multicenter open-label, phase 2 clinical trial of 42 chemotherapy-naive patients with progressing mCRPC after treatment with abiraterone acetate and/or enzalutamide was conducted from June 24, 2013, to June 10, 2016. Intervention: Treatment with BIND-014 at a dosage of 60 mg/m2 was given intravenously on day 1 of 21-day cycles in combination with prednisone until disease progression or unacceptable toxic effects occurred. Main Outcomes and Measures: The primary end point was radiographic progression-free survival according to Prostate Cancer Working Group 2 recommendations and Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary end points included prostate-specific antigen (PSA) response (≥50% reduction from baseline) and changes in CTC number (from ≥5 to <5 cells per 7.5 mL of blood) (CellSearch). Changes in CTC number based on PSMA expression levels on CTCs were also evaluated (Epic Sciences). Results: Among the 42 patients (81% white), th...