Open-label phase II study evaluating the efficacy and safety of two doses of pertuzumab in castrate chemotherapy-naive patients with hormone-refractory prostate cancer

Purpose To determine the prostate-specific antigen (PSA) 50% decline rate within 24 weeks of starting treatment with single-agent pertuzumab in castrate patients with hormone-refractory prostate cancer (HRPC). Patients and Methods Two independent Simon's two-stage designs were used to evaluate two doses of pertuzumab administered intravenously once every 3 weeks. An interim analysis of the first 23 assessable patients in the first cohort treated at 420 mg (loading dose of 840 mg) allowed termination of additional enrollment if <= three patients had a >= 50% decline in PSA after all patients had completed at least three cycles of therapy or withdrew due to insufficient therapeutic response, death, or study-related toxicity before completing three cycles. A second cohort of patients treated at 1,050 mg could be enrolled with the same design, and if more than three patients had a >= 50% decline in PSA, 27 more patients would be treated at 1,050 mg. Results Sixty-eight castrate, chemotherapy-naive men with HRPC were enrolled. A total of 35 patients were treated at 420 mg; no PSA declines >= 50% were observed at the interim analysis and recruitment was stopped. A total of 33 patients were then treated at 1,050 mg, and no PSA declines >= 50% were observed at the interim analysis. Pertuzumab was well tolerated. Conclusion Pertuzumab has no clinically significant single-agent activity in castrate patients with HRPC at either of the tested dose levels. This may reflect the continued presence of significant levels of intraprostatic androgen driving androgen receptor signaling.