Originally published as JCO Early Release 10.1200/JCO.2007.14.2646 on December 15 2008

This Article Full Text Full Text (PDF) 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 Baselga, J. Articles by Galbraith, S. Search for Related Content PubMed PubMed Citation Articles by Baselga, J. Articles by Galbraith, S. Social Bookmarking                            What's this?

Phase II Genomics Study of Ixabepilone as Neoadjuvant Treatment for Breast Cancer

From the Vall d'Hebron University Hospital, Barcelona; Hospital Universitario Arnau Vilanova, Lleida; Hospital Universitario 12 de Octobre, Madrid, Spain; Fondazione Istituto Nazionale dei Tumori, Milan, Italy; St Petersburg City Oncology Hospital, St Petersburg; Moscow Oncological Hospital No. 62; Blokhin Cancer Research Center, Moscow, Russian Federation; Medical University of Vienna; Wilhelminenspital, Vienna, Austria; University of Newcastle Upon Tyne, Newcastle Upon Tyne, United Kingdom; Karolinska Institute, Stockholm, Sweden; and Clinical Discovery, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ.

Corresponding author: José Baselga, MD, Medical Oncology Service, Vall d'Hebron University Hospital, P. Vall d'Hebron 119-129, 08035 Barcelona, Spain; e-mail: jbaselga{at}vhebron.net.

Purpose This phase II study evaluated the efficacy and safety of ixabepilone as neoadjuvant therapy for invasive breast cancer not amenable to breast conservation surgery. Gene expression studies were undertaken using genes that were identified as potentially associated with sensitivity/resistance to ixabepilone in prior preclinical investigations.

Patients and Methods Patients with invasive breast cancer 3 cm were eligible. Ixabepilone 40 mg/m² was administered as a 3-hour intravenous infusion on day 1 of a 21-day cycle for four or fewer cycles.

Results One hundred sixty-one patients were treated. The overall complete pathologic response (pCR) rate was 18% in breast and 29% in estrogen receptor (ER) –negative patients. Gene expression data were available for 134 patients. ER gene expression (ER1) was inversely related to pCR in breast and had a positive predictive value (PPV) of 37% and negative predictive value (NPV) of 92%. A 10-gene penalized logistic regression (PLR) model developed from 200 genes predictive of ixabepilone sensitivity in preclinical experiments included ER and tau and had higher PPV (45%) and comparable NPV (89%) to ER1. Grade 3 to 4 adverse events (AEs) were reported for 32% of patients. Except for neutropenia and leukopenia, all grade 3 to 4 AEs occurred in 3% of patients. Reversible peripheral neuropathy was experienced by 3% of patients.

Conclusion ER, microtubule-associated protein tau, and a 10-gene PLR model that included ER were identified as predictors of ixabepilone-induced pCR. Results indicate an inverse relation between ER expression levels and ixabepilone sensitivity. Neoadjuvant ixabepilone demonstrated promising activity and a manageable safety profile in patients with invasive breast tumors.

Supported by Bristol-Myers Squibb. The authors vouch for the completeness and accuracy of results presented.

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:

				A. Goldhirsch, J. N. Ingle, R. D. Gelber, A. S. Coates, B. Thurlimann, H.-J. Senn, and Panel members Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2009 Ann. Onc., August 1, 2009; 20(8): 1319 - 1329. [Abstract] [Full Text] [PDF]