Phase II Randomized Study of Ixabepilone Versus Observation in Patients With Significant Residual Disease After Neoadjuvant Systemic Therapy for HER2-Negative Breast Cancer.

Abstract

BACKGROUND:

Residual disease (RD) after neoadjuvant chemotherapy carries an increased risk for recurrence. Ixabepilone has activity in anthracycline/taxanes-resistant breast cancer. We explored adjuvant ixabepilone in patients with significant RD HER2-negative breast cancer.

METHODS:

A phase II study in patients with residual cancer burden II or III randomized to ixabepilone versus observation was conducted. Circulating tumor cells (CTCs) were measured at baseline and at 9 and 18 weeks. Survival probabilities were estimated by Kaplan-Meier product limit. Toxicities were reported as proportions in the ixabepilone arm.

RESULTS:

Accrual was stopped because of ixabepilone toxicity. Sixty-seven patients were registered; 43 were randomized, 19 received ixabepilone, and 24 went to observation. One patient (9.1%) in the observation arm versus 2 patients (18.2%) in the ixabepilone arm had CTCs at 18 weeks (P = 1.0). Three-year recurrence-free survival and overall survival were 94% and 82%, and 100% and 79% in the observation and ixabepilone arms (P = .35 and .18), respectively. Most common adverse events (AEs) included fatigue, pain, neuropathy, constipation, nausea, rash, anorexia, and diarrhea. Serious AEs included pain (63.2%), fatigue (31.6%), and neuropathy (31.6%).

CONCLUSIONS:

Adjuvant ixabepilone in patients with significant RD after neoadjuvant chemotherapy was difficult to administer because of AEs and did not change the presence of CTC or affect survival outcomes. NCT00877500.

• Authors: Ana M Gonzalez-Angulo, Xiudong Lei, Richardo H Alvarez, Majorie C Green, James L Murray, Vicente Valero, Kimberly B Koenig, Nuhad K Ibrahim, Jennifer K Litton, Lakshmy Nair, Savitri Krishnamurthy, Gabriel N Hortobagyi, Funda Meric-Bernstam
• Journal: Clinical breast cancer (Clin Breast Cancer) Vol. 15 Issue 5 Pg. 325-31 (Oct 2015) ISSN: 1938-0666 [Electronic] United States
• PMID: 25913905 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Epothilones
• Receptor, ErbB-2
• ixabepilone

Topics

• Adult
• Antineoplastic Agents (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Breast Neoplasms (drug therapy, metabolism)
• Chemotherapy, Adjuvant
• Dose-Response Relationship, Drug
• Drug Resistance, Neoplasm (drug effects)
• Epothilones (administration & dosage, adverse effects)
• Female
• Humans
• Middle Aged
• Neoplasm Metastasis
• Receptor, ErbB-2 (metabolism)