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

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204 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4324-4332
Number of pages9
JournalJournal of Clinical Oncology
Volume24
Issue number26
DOIs
StatePublished - Sep 10 2006
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Gordon, M. S., Matei, D., Aghajanian, C., Matulonis, U. A., Brewer, M., Fleming, G. F., Hainsworth, J. D., Garcia, A. A., Pegram, M. D., Schilder, R. J., Cohn, D. E., Roman, L., Derynck, M. K., Ng, K., Lyons, B., Allison, D. E., Eberhard, D. A., Pham, T. Q., Dere, R. C., & Karlan, B. Y. (2006). Clinical activity of pertuzumab (rhuMAb 2C4), a HER dimerization inhibitor, in advanced ovarian cancer: Potential predictive relationship with tumor HER2 activation status. Journal of Clinical Oncology, 24(26), 4324-4332. https://doi.org/10.1200/JCO.2005.05.4221