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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

Johann Sebastian de Bono, Joaquim Bellmunt, Gerhardt Attard, Jean Pierre Droz, Kurt Miller, Aude Flechon, Cora Sternberg, Chris Parker, Gerhard Zugmaier, Veronica Hersberger-Gimenez, Louise Cockey, Malcolm Mason, John Graham

From the Drug Development Unit and Department of Academic Urology, Royal Marsden Hospital, Surrey; Department of Oncology, University of Wales College Hospital, Wales; Department of Oncology, Bristol Oncology Centre, Bristol, United Kingdom; University Hospital Vall de Hebron, Department of Medical Oncology, Barcelona, Spain; Centre Leon Berard Department of Oncology, Lyon, France; University Clinic Benjamin Franklin, Department of Urology, Urological Clinic, FU Berlin, Germany; F. Hoffmann-La Roche, Department of Oncology, Basel, Switzerland; and San Camillo and Forlanini Hospitals, Department of Medical Oncology, Rome, Italy

Address reprint requests to Johann S. de Bono, MB, ChB, FRCP, MSc, PhD, Centre for Cancer Therapeutics, Institute for Cancer Research, Royal Marsden Hospital, Downs Rd, Sutton, Surrey SM2 5PT, United Kingdom; e-mail: jdebono{at}icr.ac.uk

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.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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