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.

Abstract

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: 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
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 25 Issue 3 Pg. 257-62 (Jan 20 2007) ISSN: 1527-7755 [Electronic] United States
• PMID: 17235043 (Publication Type: Clinical Trial, Phase II, Journal Article)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents, Hormonal
• Prostate-Specific Antigen
• pertuzumab

Topics

• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents, Hormonal (pharmacology)
• Drug Resistance, Neoplasm
• Humans
• Male
• Middle Aged
• Prostate-Specific Antigen (blood)
• Prostatic Neoplasms (blood, drug therapy, pathology)
• Treatment Outcome