PSMA-targeted nanoparticle agent is active against mCRPC
medwireNews: Research published in JAMA Oncology points to the efficacy of a prostate-specific membrane antigen (PSMA)-directed docetaxel-containing nanoparticle in patients with metastatic castration-resistant prostate cancer (mCRPC).
The agent – called BIND-014 – “is enriched in the tumor microenvironment and can be internalized on binding to a PSMA-expressing cell, enabling the preferential delivery of docetaxel to the tumor,” explain the researchers, adding that such optimized delivery of chemotherapy should “maximize therapeutic benefit while reducing off-target toxic effects.”
Forty-two men with mCRPC that had progressed after treatment with abiraterone acetate and/or enzalutamide were given intravenous BIND-014 at a dose of 60 mg/m2 plus prednisone 5 mg twice daily on the first day of each 21-day cycle.
Radiographic progression-free survival (PFS) was a median of 9.9 months, and the probability of remaining progression-free for at least 6 months was 78%, which exceeded the prespecified definition of success, that is, a radiographic PFS rate at 6 months of more than 65%.
Twelve (30%) of the 40 men with available prostate-specific antigen (PSA) data achieved a decrease of at least 50% in PSA levels relative to baseline, and six (32%) of the 19 participants with measurable disease responded, with one complete and five partial responses. A further nine men had stable disease, giving a disease control rate of 79%.
Noting that decrease in circulating tumor cell (CTC) counts has been linked to improved overall survival, the team reports that of the 26 participants who had an unfavorable CTC count at baseline (≥5 CTCs per 7.5 mL of blood), half achieved either a favorable CTC count (<5 CTCs) or undetectable CTCs after treatment with BIND-014.
“The agent was also well tolerated,” with adverse events generally tending to be grade 1 or 2, and not much need for dose reductions due to treatment-related toxicity, say Karen Autio (Memorial Sloan Kettering Cancer Center, New York, USA) and colleagues.
Nonetheless, a third of patients experienced neuropathy, which is similar to the incidence with a standard docetaxel regimen, and half reported low-grade nausea, they add.
“These toxic reactions suggest that treatment with BIND-014 is associated with off-target effects on healthy tissue.”
Autio et al say that while many aspects of the BIND-014 results are promising, “standard therapy with docetaxel is widely used and effective in treating this disease, and as a natural comparator for a phase 3 randomized clinical trial with BIND-014, it sets a high bar for efficacy in an unselected population.”
They, therefore, believe that a biomarker that enables the selection of patients who might benefit from BIND-014 therapy could be useful.
One such marker could be PSMA-positive CTCs, say the researchers. Among a subset of 14 patients with serial blood samples, PSMA-positive CTCs decreased from a median of 3.4 CTCs/mL at baseline to 1.14 CTCs/mL at week 3 following treatment and to 0.0 CTCs/mL at week 9.
“Selecting patients with pretreatment PSMA-positive CTCs remains a promising strategy for PSMA-targeted therapy that could hold a therapeutic and toxicity advantage over docetaxel-based chemotherapy,” the team concludes.
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