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Sub-category:
Ovarian Cancer
Category:
Gynecologic Cancer
Meeting:
2008 ASCO Annual Meeting
Session Type and Session Title:
General Poster Session, Gynecologic Cancer
Abstract No:
5552
Citation:
J Clin Oncol 26: 2008 (May 20 suppl; abstr 5552)
Author(s):
L. Amler, S. Makhija, T. Januario, U. A. Matulonis, A. Strauss, D. S. Dizon, M. X. Sliwkowski, M. Dolezal, B. Tong, V. Paton
Abstract:
Background: Pertuzumab (P) is a humanized monoclonal antibody that inhibits HER2 heterodimerization. A randomized phase II trial (N=130) of pertuzumab + gemcitabine vs. gemcitabine + placebo in patients with platinum-resistant (CDDP-R) epithelial ovarian cancer (EOC) suggested that pertuzumab could prolong PFS (HR 0.66, 95% CI 0.43, 1.03) and that the duration of PFS may be associated with HER3 gene expression. Final data for overall survival from this trial are presented. Methods: Patients with CDDP-R EOC were randomized to G+P or G+placebo. Treatment was given until progression or until unacceptable toxicity. The primary endpoint was PFS. A secondary objective was to evaluate efficacy outcomes in patients with HER2 activation-related expression profiles. A qRT-PCR assay using archival formalin-fixed paraffin-embedded tissue (FFPET) allowed mRNA expression analysis of HER pathway genes, including HER1, HER2, HER3, amphiregulin, and betacellulin. Outcomes were described by low gene expression (<median) and by high gene expression (>median). Results: Of the 5 biomarkers tested, only HER3 gene expression suggested a patient subgroup with a differential PFS and OS outcome based upon low vs. high results. Final PFS and OS outcomes for all patients and by qRT-PCR HER3 outcomes are as follows in the table below. Conclusions: This exploratory analysis suggests that low tumor HER3 gene expression levels may be prognostic in patients with CDDP-R EOC. Pertuzumab treatment may add to gemcitabine's clinical activity in patients whose tumors have low HER3 gene expression. These data suggest that HER3 mRNA expression levels may be a potential prognostic and predictive diagnostic biomarker. | G + P | G + Placebo | Hazard Ratio (95% CI) | | PFS (median months) | | | | | All Patients (n=130) | 2.9 | 2.6 | 0.66* (0.43, 1.03) | | Low HER3 (N=61) | 5.3 | 1.4 | 0.34 (0.18, 0.63) | | High HER3 (N=61) | 2.8 | 5.5 | 1.48 (0.83, 2.63) | | OS (median months) | | | | | All Patients (n=130) | 13.0 | 13.1 | 0.91* (0.58, 1.41) | | Low HER3 (N=61) | 11.8 | 8,4 | 0.62 (0.35, 1.11) | | High HER3 (N=61) | 16.1 | 18.2 | 1.59 (0.8, 3.2) | | *All-patient analyses were stratified by ECOG status, disease measurability and # prior regimens for CDDP-R disease. |
Abstract Disclosures
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy
and are designated with a caret symbol (^) here and in the print version.
 Associated Presentation(s):
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1. HER pathway gene expression analysis in a phase II study of pertuzumab + gemcitabine vs. gemcitabine + placebo in patients with platinum-resistant epithelial ovarian cancer.
Meeting:
2008 ASCO Annual Meeting
Presenter:
Lukas Amler
Session:
Gynecologic Cancer
(General Poster Session)
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Other Abstracts in this Sub-Category:
Abstracts by L. Amler:
Presentations by L. Amler:
Educational Book Manuscripts by L. Amler:
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