Autio KA, et al. - In patients with metastatic castration-resistant prostate cancer (mCRPC), researchers tested the safety and effectiveness of BIND-014 (a prostate-specific membrane antigen [PSMA]-directed docetaxel-containing nanoparticle). They found that treatment with BIND-014 was active and well tolerated in patients with chemotherapy-naive mCRPC. Findings also revealed that antitumor activity might be associated with PSMA expression levels on circulating tumor cells (CTCs), which suggests that patients who are likely to benefit from this treatment can be identified before treatment is started. Grade 1 or 2 fatigue, nausea, neuropathy, and neutropenic fever were included treatment-related adverse events.

Methods

• This was a multicenter open-label, phase 2 clinical trial that included 42 chemotherapy-naive patients with progressing mCRPC after treatment with abiraterone acetate and/or enzalutamide; this study was led from June 24, 2013, to June 10, 2016.
• Until disease progression or unacceptable toxic effects occurred, 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.
• Radiographic progression-free survival (PFS) was the primary endpoint according to Prostate Cancer Working Group 2 recommendations and Response Evaluation Criteria in Solid Tumors, version 1.1.
• 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) were included secondary end points.
• Researchers also assessed changes in CTC number based on PSMA expression levels on CTCs.

Results

• Median study participant age was 66 years, and median number of doses received was 6 among the 42 patients (81% white).
• PSA response was evident in 12 of 40 (30%) patients, measurable disease response in 6 of 19 (32%), and CTC conversions in 13 of 26 (50%).
• It was noted that median radiographic PFS was 9.9 months.
• CTCs were detected in 16 of 18 patients (89%) with use of the Epic Sciences non-EPCAM-based CTC detection platform.
• A total of 11 of 18 (61%) participants had CTCs with PSMA expression above the analytical threshold level (PSMA positive) at baseline (range, 0.4-72.4 CTCs/mL).
• PSMA-positive CTCs were preferentially reduced after treatment.
• Grade 1 or 2 fatigue (29 of 42 patients [69%]), nausea (23 [55%]), neuropathy (14 [33%]), and neutropenic fever (1 [2%]) were included treatment-related adverse events.