In a phase II trial reported in the Journal of Clinical Oncology, McKay et al found a trend toward improved pathologic response or minimal residual disease with the addition of neoadjuvant abiraterone and prednisone to enzalutamide and leuprolide prior to radical prostatectomy in patients with locally advanced prostate cancer.
In the open-label multicenter trial, 75 patients were randomly assigned to 2:1 to abiraterone at 1,000 mg/d, enzalutamide at 160 mg/d, leuprolide at 22.5 mg every 12 weeks, and prednisone at 5 mg/d (ELAP; n = 50) or enzalutamide plus leuprolide (EL; n = 25) for 24 weeks followed by radical prostatectomy. Patients had a Gleason score of 4 + 3 = 7 or greater, prostate-specific antigen (PSA) > 20 ng/mL, or T3 disease on prostate magnetic resonance imaging. Lymph nodes were required to be < 20 mm.
The primary endpoint was pathologic complete response or minimal residual disease defined as residual tumor ≤ 5 mm on central pathology review. Most patients (87%) had high-risk disease on National Comprehensive Cancer Network (NCCN®) criteria.
The pathologic complete response or minimal residual disease rate was 30% (15 of 50 patients; 10% pathologic complete response) in the ELAP group vs 16% (n = 4 of 25 patients; 8% pathologic complete response) in the EL group (P = .263). Rates of ypT3 disease (50% vs 56%), positive margins (18% vs 12%), and positive lymph nodes (10% vs 12%) were similar between the groups. PSA nadirs before surgery were 0.03 vs 0.02 ng/mL.
Residual tumors in the two groups had comparable levels of ERG, PTEN, androgen receptor PSA, and glucocorticoid receptor expression. PTEN loss rate was significantly higher in ERG-positive tumors (65% v 29%; P = .017), and combined tumor ERG-positivity and PTEN loss were associated with more extensive residual tumor at radical prostatectomy.
Treatment was well-tolerated. Treatment-related adverse events were similar in the two groups, except for a greater incidence of any grade and grade 3 hypertension, increased alanine transaminase, and increased aspartate transaminase in the ELAP group. No treatment-related grade 4 adverse events were observed.
The investigators concluded, “Neoadjuvant hormone therapy followed by [radical prostatectomy] in locally advanced prostate cancer resulted in favorable pathologic responses in some patients, with a trend toward improved pathologic outcomes with ELAP. Longer follow-up is necessary to evaluate the impact of therapy on recurrence rates. The potential association of ERG and PTEN alterations with worse outcomes warrants additional investigation.”
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