In a phase II trial reported in JAMA Oncology, Autio et al found that prostate-specific membrane antigen (PSMA)–targeted docetaxel nanoparticle (BIND-014) treatment was active in patients with metastatic castration-resistant prostate cancer (mCRPC).
In the multicenter trial, 42 chemotherapy-naive patients progressing after treatment with abiraterone (Zytiga) or enzalutamide (Xtandi) were enrolled between June 2013 and June 2016 and treated with BIND-014 at 60 mg/m2 intravenously on day 1 of 21-day cycles in combination with prednisone 5 mg twice daily until disease progression or unacceptable toxicity.
The primary endpoint was radiographic progression-free survival.
Median radiographic progression-free survival was 9.9 months. Prostate-specific antigen (PSA) response (≥ 50% from baseline) was observed in 12 (30%) of 40 patients, and measureable disease response was observed in 6 (32%) of 19 patients. Circulating tumor cell (CTC) conversion (from ≥ 5 to < 5 cells per 7.5 mL of blood) was observed in 13 (50%) of 26 patients. Assessment of changes in CTC number based on levels of CTC PSMA expression using a non–EPCAM-based detection platform showed that 11 of 18 patients with detected CTCs had CTCs with PSMA expression above the analytical threshold level at baseline (PSMA-positive). Among 14 evaluable PSMA-positive patients, median PSMA-positive CTC counts at weeks 3 vs 9 were 1.14 CTCs vs 0 CTCs; only 2 patients had week 9 PSMA-positive CTC concentrations greater than baseline PSMA-positive CTC counts.
The most common treatment-related adverse events of any grade were fatigue (69%), nausea (55%), and diarrhea (45%); neuropathy occurred in 33% of patients. Febrile neutropenia occurred in one patient. The most common grade 3 or 4 treatment-related adverse events were lymphopenia (12%), anemia (7%), and fatigue and nausea (5% each).
The investigators concluded, “These findings suggest that treatment with BIND-014 is active and well tolerated in patients with chemotherapy-naive mCRPC. Antitumor activity may be related to PSMA expression levels on CTCs, which suggests that patients who are likely to benefit from this treatment can be identified before treatment is initiated.”
The study was supported by BIND Therapeutics, Inc., and by grants from the National Cancer Institute.
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