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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Agus, D. B. Articles by Scher, H. I. Search for Related Content PubMed PubMed Citation Articles by Agus, D. B. Articles by Scher, H. I.

Efficacy and Safety of Single-Agent Pertuzumab (rhuMAb 2C4), a Human Epidermal Growth Factor Receptor Dimerization Inhibitor, in Castration-Resistant Prostate Cancer After Progression From Taxane-Based Therapy

David B. Agus, Christopher J. Sweeney, Michael J. Morris, David S. Mendelson, Douglas G. McNeel, Frederick R. Ahmann, Jin Wang, Mika K. Derynck, Kimmie Ng, Benjamin Lyons, David E. Allison, Michael W. Kattan, Howard I. Scher

From the Cedars-Sinai Prostate Cancer Center, Los Angeles; Genentech Inc, South San Francisco, CA; Indiana University Medical Center, Indianapolis, IN; Memorial Sloan-Kettering Cancer Center, New York, NY; Premiere Oncology of Arizona, Scottsdale; Arizona Cancer Center, Tucson, AZ; University of Wisconsin, Madison, WI; and the Cleveland Clinic Foundation, Cleveland, OH

Address reprint requests to David B. Agus, MD, Cedars-Sinai Prostate Cancer Center, 8631 West Third St, Suite 215E, Los Angeles, CA 90048; e-mail: David.Agus{at}cshs.org

PURPOSE: Pertuzumab represents a new class of targeted anticancer agents, human epidermal growth factor receptor (HER) dimerization inhibitors. The aim of this single-arm phase II clinical study was to assess the efficacy and safety of single-agent pertuzumab in castration-resistant prostate cancer (CRPC) patients who had experienced progression after prior chemotherapy.

PATIENTS AND METHODS: Patients received pertuzumab every 3 weeks. All castration-resistant patients had experienced progression after at least one taxane-based regimen. Patients received a loading dose of 840 mg pertuzumab (cycle 1) followed by 420 mg for subsequent cycles. The primary end point was overall response and safety. A separate retrospective analysis of actual survival time versus predicted survival time for a patient population with comparable prognostic features was performed.

RESULTS: Patients were enrolled (N = 42) and treated (n = 41). No patients had complete or partial response (as defined by Response Evaluation Criteria in Solid Tumors Group or 50% decline in prostate-specific antigen). Of 30 efficacy-assessable patients, five had stable disease (SD) for at least 23 weeks; one of five had SD for 36 weeks. Pertuzumab was well tolerated; diarrhea was the most common adverse effect (61.0%, grades 1 to 3). Retrospective analysis of survival using a validated nomogram suggested that survival was prolonged with pertuzumab treatment, compared with historic controls with similar baseline prognostic features.

CONCLUSION: Pertuzumab was well tolerated and resulted in no objective responses, but several patients had SD more than 23 weeks from a heavily pretreated population. Retrospective analysis suggested prolonged median survival time with pertuzumab compared with historical controls. Thus, inhibition of HER dimerization may have clinical utility in CRPC patients.

Supported by Genentech Inc, South San Francisco, CA.

Presented in part at the 41st Annual Meeting of the American Society of Clinical Oncology, May 13-17, 2005, Orlando, FL.

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

This article has been cited by other articles:

				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]

				S. R. Chinni, H. Yamamoto, Z. Dong, A. Sabbota, R. D. Bonfil, and M. L. Cher CXCL12/CXCR4 Transactivates HER2 in Lipid Rafts of Prostate Cancer Cells and Promotes Growth of Metastatic Deposits in Bone Mol. Cancer Res., March 1, 2008; 6(3): 446 - 457. [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]

				C. Festuccia, G. L. Gravina, P. Muzi, R. Pomante, L. Ventura, R. L Vessella, C. Vicentini, and M. Bologna Bicalutamide increases phospho-Akt levels through Her2 in patients with prostate cancer Endocr. Relat. Cancer, September 1, 2007; 14(3): 601 - 611. [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]