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 Journal Article

  

Authors:	Agus, D. B.; Sweeney, C. J.; Morris, M. J.; Mendelson, D. S.; McNeel, D. G.; Ahmann, F. R.; Wang, J.; Derynck, M. K.; Ng, K.; Lyons, B.; Allison, D. E.; Kattan, M. W.; Scher, H. I.
Article Title:	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
Abstract:	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.
Keywords:	prednisone; chemotherapy; mitoxantrone; androgen receptor; tyrosine kinase; erbb2; modulation; expression; phase-ii; ii clinical-trials
Journal Title:	Journal of Clinical Oncology
Volume:	25
Issue:	6
ISSN:	0732-183X
Publisher:	American Society of Clinical Oncology
Date Published:	2007-02-20
Start Page:	675
End Page:	681
Language:	English
ACCESSION:	WOS:000244384000012
DOI:	10.1200/jco.2006.07.0649
PROVIDER:	wos
PUBMED:	17308272
Notes:	--- - Article; Proceedings Paper - 41st Annual Meeting of the American-Society-of-Clinical-Oncology - MAY 13-17, 2005 - Orlando, FL - "Source: Wos"

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