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Gordon MS , Matei D , Aghajanian C , Matulonis UA , Brewer M , Fleming GF , Hainsworth JD , Garcia AA , Pegram MD , Schilder RJ , Cohn DE , Roman L , Derynck MK , Ng K , Lyons B , Allison DE , Eberhard DA , Pham TQ , Dere RC , Karlan BY
Clinical activity of pertuzumab (rhuMAb 2C4), a HER dimerization inhibitor, in advanced ovarian cancer: potential predictive relationship with tumor HER2 activation status
J Clin Oncol. 2006 Sep 10;24(26) :4324-32
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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 > or = 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.
Notes
Gordon, Michael S Matei, Daniela Aghajanian, Carol Matulonis, Ursula A Brewer, Molly Fleming, Gini F Hainsworth, John D Garcia, Agustin A Pegram, Mark D Schilder, Russell J Cohn, David E Roman, Lynda Derynck, Mika K Ng, Kimmie Lyons, Benjamin Allison, David E Eberhard, David A Pham, Thinh Q Dere, Randall C Karlan, Beth Y Clinical Trial, Phase II Multicenter Study Research Support, Non-U.S. Gov't United States Journal of clinical oncology : official journal of the American Society of Clinical Oncology J Clin Oncol. 2006 Sep 10;24(26):4324-32. Epub 2006 Aug 8.