Originally published as JCO Early Release 10.1200/JCO.2005.05.4221 on August 8 2006

This Article Full Text Full Text (PDF) Publisher's Note Erratum (v26,p2793) 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 Gordon, M. S. Articles by Karlan, B. Y. Search for Related Content PubMed PubMed Citation Articles by Gordon, M. S. Articles by Karlan, B. Y. Social Bookmarking                            What's this?

Clinical Activity of Pertuzumab (rhuMAb 2C4), a HER Dimerization Inhibitor, in Advanced Ovarian Cancer: Potential Predictive Relationship With Tumor HER2 Activation Status

Michael S. Gordon, Daniela Matei, Carol Aghajanian, Ursula A. Matulonis, Molly Brewer, Gini F. Fleming, John D. Hainsworth, Agustin A. Garcia, Mark D. Pegram, Russell J. Schilder, David E. Cohn, Lynda Roman, Mika K. Derynck, Kimmie Ng, Benjamin Lyons, David E. Allison, David A. Eberhard, Thinh Q. Pham, Randall C. Dere, Beth Y. Karlan

From the Arizona Cancer Center, Tuscon and Scottsdale, AZ; Indiana University, Indianapolis, IN; Memorial Sloan-Kettering Cancer Center, New York, NY; Dana-Farber/Harvard Cancer Institute, Boston, MA; University of Chicago, Chicago, IL; Sarah Cannon Research Institute, Nashville, TN; Cedars-Sinai Medical Center; UCLA Medical Center, Los Angeles, CA; USC Norris Comprehensive Cancer Center; Genentech Inc, South San Francisco, CA; Fox Chase Cancer Center; James Cancer Hospital, Ohio State University, Columbus, OH.

Address reprint requests to Beth Y. Karlan, MD, Cedars-Sinai Medical Center, Women's Cancer Research Institute, 8700 Beverly Blvd, #290W, Los Angeles, CA 90048; e-mail: Beth.Karlan{at}cshs.org

Purpose Ovarian cancers (OCs) frequently have HER2 activation in the absence of HER2 overexpression. Pertuzumab, a humanized antibody that prevents HER2 dimerization and inhibits multiple HER-mediated pathways, was studied in a phase II, multicenter trial in advanced, refractory OC.

Patients and Methods Sixty-one patients (cohort 1) with relapsed OC received a loading dose of 840 mg pertuzumab intravenously followed by 420 mg every 3 weeks; 62 patients (cohort 2) received 1,050 mg every 3 weeks. Response rate was the primary end point. Fresh tumor biopsies were obtained in cohort 1 to assay for phosphorylated HER2 (pHER2).

Results Median age was 57 years and median number of prior chemotherapy regimens was five. Fifty-five patients in cohort 1 and 62 patients in cohort 2 were assessable for efficacy. There were five partial responses (response rate [RR] = 4.3%; 95% CI, 1.7% to 9.4%), eight patients (6.8%) with stable disease (SD) lasting at least 6 months, and 10 patients with CA-125 reduction of at least 50% (includes two partial responses and four patients with SD 6 months; total clinical activity, 14.5%). Median progression-free survival (PFS) was 6.6 weeks. Eight of 28 tumor biopsies (28.6%) were pHER2+ by enzyme-linked immunosorbent assay (ELISA; without gene amplification). Median PFS for pHER2+ patients was 20.9 weeks (n = 8) versus 5.8 weeks for pHER2– (n = 20; P = .14) and 9.1 weeks for unknown pHER2 status (n = 27). Pertuzumab was well tolerated with diarrhea in 69.1% (11.4% grade 3, no grade 4). Five patients had asymptomatic left ventricular ejection fraction decreases to less than 50% (one confirmed by central facility).

Conclusion Pertuzumab is well tolerated with a RR of 4.3% in heavily-pretreated OC patients. Further studies on pHER2 as a diagnostic are warranted.

published online ahead of print at www.jco.org on August 7, 2006.

Supported by Genentech Inc, South San Francisco, CA.

Presented in part at the 41st Annual Meeting of the American Society of Clinical Oncology, Orlando, FL, May 13-17, 2005, and the 34th Annual Meeting of the Western Association of Gynecologic Oncologists, Santa Fe, NM, June 15-18, 2005.

Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org.

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?

This article has been cited by other articles:

				Y. Nagumo, D. Faratian, P. Mullen, D. J. Harrison, M. Hasmann, and S. P. Langdon Modulation of HER3 Is a Marker of Dynamic Cell Signaling in Ovarian Cancer: Implications for Pertuzumab Sensitivity Mol. Cancer Res., September 1, 2009; 7(9): 1563 - 1571. [Abstract] [Full Text] [PDF]

				S. Banerjee and M. Gore The Future of Targeted Therapies in Ovarian Cancer Oncologist, July 1, 2009; 14(7): 706 - 716. [Abstract] [Full Text] [PDF]

				C. L. Arteaga, A. O'Neill, S. L. Moulder, M. Pins, J. A. Sparano, G. W. Sledge, and N. E. Davidson A Phase I-II Study of Combined Blockade of the ErbB Receptor Network with Trastuzumab and Gefitinib in Patients with HER2 (ErbB2)-Overexpressing Metastatic Breast Cancer Clin. Cancer Res., October 1, 2008; 14(19): 6277 - 6283. [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]

				J. Albanell, C. Montagut, E. T. Jones, L. Pronk, B. Mellado, J. Beech, P. Gascon, G. Zugmaier, M. Brewster, M. P. Saunders, et al. A Phase I Study of the Safety and Pharmacokinetics of the Combination of Pertuzumab (rhuMab 2C4) and Capecitabine in Patients with Advanced Solid Tumors Clin. Cancer Res., May 1, 2008; 14(9): 2726 - 2731. [Abstract] [Full Text] [PDF]

				R. S. Herbst, A. M. Davies, R. B. Natale, T. P. Dang, J. H. Schiller, L. L. Garland, V. A. Miller, D. Mendelson, A. D. Van den Abbeele, Y. Melenevsky, et al. Efficacy and Safety of Single-Agent Pertuzumab, a Human Epidermal Receptor Dimerization Inhibitor, in Patients with Non Small Cell Lung Cancer Clin. Cancer Res., October 15, 2007; 13(20): 6175 - 6181. [Abstract] [Full Text] [PDF]

				B. Li, D. J. Allendorf, R. Hansen, J. Marroquin, D. E. Cramer, C. L. Harris, and J. Yan Combined Yeast {beta}-Glucan and Antitumor Monoclonal Antibody Therapy Requires C5a-Mediated Neutrophil Chemotaxis via Regulation of Decay-Accelerating Factor CD55 Cancer Res., August 1, 2007; 67(15): 7421 - 7430. [Abstract] [Full Text] [PDF]

				L. Martin and R. Schilder Novel Approaches in Advancing the Treatment of Epithelial Ovarian Cancer: The Role of Angiogenesis Inhibition J. Clin. Oncol., July 10, 2007; 25(20): 2894 - 2901. [Abstract] [Full Text] [PDF]

				S. D. Allen, J. T. Garrett, S. V. Rawale, A. L. Jones, G. Phillips, G. Forni, J. C. Morris, R. G. Oshima, and P. T. P. Kaumaya Peptide Vaccines of the HER-2/neu Dimerization Loop Are Effective in Inhibiting Mammary Tumor Growth In Vivo J. Immunol., July 1, 2007; 179(1): 472 - 482. [Abstract] [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]

				P. Mullen, D. A. Cameron, M. Hasmann, J. F. Smyth, and S. P. Langdon Sensitivity to pertuzumab (2C4) in ovarian cancer models: cross-talk with estrogen receptor signaling Mol. Cancer Ther., January 1, 2007; 6(1): 93 - 100. [Abstract] [Full Text] [PDF]