This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by de Bono, J. S. Articles by Graham, J. Search for Related Content PubMed PubMed Citation Articles by de Bono, J. S. Articles by Graham, J. Related Articles Related Correspondence Social Bookmarking                            What's this?

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.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Correspondence

• Targeting Human Epidermal Growth Factor Receptor 2: It Is Time to Kill Kinase Death Human Epidermal Growth Factor Receptor 3
  Javier A. Menendez and Ruth Lupu
  JCO 2007 25: 2496-2498 [Full Text]

This article has been cited by other articles:

				G. Attard, A. H.M. Reid, R. A'Hern, C. Parker, N. B. Oommen, E. Folkerd, C. Messiou, L. R. Molife, G. Maier, E. Thompson, et al. Selective Inhibition of CYP17 With Abiraterone Acetate Is Highly Active in the Treatment of Castration-Resistant Prostate Cancer J. Clin. Oncol., August 10, 2009; 27(23): 3742 - 3748. [Abstract] [Full Text] [PDF]

				L. Aurisicchio, D. Peruzzi, A. Conforti, S. Dharmapuri, A. Biondo, S. Giampaoli, A. Fridman, A. Bagchi, C. T. Winkelmann, R. Gibson, et al. Treatment of Mammary Carcinomas in HER-2 Transgenic Mice through Combination of Genetic Vaccine and an Agonist of Toll-Like Receptor 9 Clin. Cancer Res., March 1, 2009; 15(5): 1575 - 1584. [Abstract] [Full Text] [PDF]

				G. Gravis, F. Bladou, N. Salem, A. Goncalves, B. Esterni, J. Walz, S. Bagattini, M. Marcy, S. Brunelle, and P. Viens Results from a monocentric phase II trial of erlotinib in patients with metastatic prostate cancer Ann. Onc., September 1, 2008; 19(9): 1624 - 1628. [Abstract] [Full Text] [PDF]

				C. C. Portera, J. M. Walshe, D. R. Rosing, N. Denduluri, A. W. Berman, U. Vatas, M. Velarde, C. K. Chow, S. M. Steinberg, D. Nguyen, et al. Cardiac Toxicity and Efficacy of Trastuzumab Combined with Pertuzumab in Patients with Trastuzumab-Insensitive Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer Clin. Cancer Res., May 1, 2008; 14(9): 2710 - 2716. [Abstract] [Full Text] [PDF]

				K. N. Chi, S. L. Ellard, S. J. Hotte, P. Czaykowski, M. Moore, J. D. Ruether, A. J. Schell, S. Taylor, C. Hansen, I. Gauthier, et al. A phase II study of sorafenib in patients with chemo-naive castration-resistant prostate cancer Ann. Onc., April 1, 2008; 19(4): 746 - 751. [Abstract] [Full Text] [PDF]

				J. Domingo-Domenech, P. L. Fernandez, X. Filella, A. Martinez-Fernandez, R. Molina, E. Fernandez, A. Alcaraz, J. Codony, P. Gascon, and B. Mellado Serum HER2 extracellular domain predicts an aggressive clinical outcome and biological PSA response in hormone-independent prostate cancer patients treated with docetaxel Ann. Onc., February 1, 2008; 19(2): 269 - 275. [Abstract] [Full Text] [PDF]

				S. F. Shariat, K. Bensalah, J. A. Karam, C. G. Roehrborn, A. Gallina, Y. Lotan, K. M. Slawin, and P. I. Karakiewicz Preoperative Plasma HER2 and Epidermal Growth Factor Receptor for Staging and Prognostication in Patients with Clinically Localized Prostate Cancer Clin. Cancer Res., September 15, 2007; 13(18): 5377 - 5384. [Abstract] [Full Text] [PDF]

				G. Attard and J. S. De Bono In Reply J. Clin. Oncol., June 10, 2007; 25(17): 2499 - 2499. [Full Text] [PDF]

				J. A. Menendez and R. Lupu Targeting Human Epidermal Growth Factor Receptor 2: It Is Time to Kill Kinase Death Human Epidermal Growth Factor Receptor 3 J. Clin. Oncol., June 10, 2007; 25(17): 2496 - 2498. [Full Text] [PDF]

				D. B. Solit and N. Rosen Targeting HER2 in Prostate Cancer: Where to Next? J. Clin. Oncol., January 20, 2007; 25(3): 241 - 243. [Full Text] [PDF]