PMID- 25913905 OWN - NLM STAT- MEDLINE DCOM- 20160620 LR - 20231111 IS - 1938-0666 (Electronic) IS - 1526-8209 (Print) IS - 1526-8209 (Linking) VI - 15 IP - 5 DP - 2015 Oct TI - Phase II Randomized Study of Ixabepilone Versus Observation in Patients With Significant Residual Disease After Neoadjuvant Systemic Therapy for HER2-Negative Breast Cancer. PG - 325-31 LID - S1526-8209(15)00068-3 [pii] LID - 10.1016/j.clbc.2015.03.004 [doi] AB - 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. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Gonzalez-Angulo, Ana M AU - Gonzalez-Angulo AM AD - Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Lei, Xiudong AU - Lei X AD - Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Alvarez, Richardo H AU - Alvarez RH AD - Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Green, Majorie C AU - Green MC AD - Genentech, South San Francisco, CA. FAU - Murray, James L AU - Murray JL AD - Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Valero, Vicente AU - Valero V AD - Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Koenig, Kimberly B AU - Koenig KB AD - Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Ibrahim, Nuhad K AU - Ibrahim NK AD - Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Litton, Jennifer K AU - Litton JK AD - Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Nair, Lakshmy AU - Nair L AD - Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Krishnamurthy, Savitri AU - Krishnamurthy S AD - Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Hortobagyi, Gabriel N AU - Hortobagyi GN AD - Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Meric-Bernstam, Funda AU - Meric-Bernstam F AD - Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address: fmeric@mdanderson.org. LA - eng SI - ClinicalTrials.gov/NCT00877500 GR - P30 CA016672/CA/NCI NIH HHS/United States GR - UL1 TR000371/TR/NCATS NIH HHS/United States PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20150324 PL - United States TA - Clin Breast Cancer JT - Clinical breast cancer JID - 100898731 RN - 0 (Antineoplastic Agents) RN - 0 (Epothilones) RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - K27005NP0A (ixabepilone) SB - IM MH - Adult MH - Antineoplastic Agents/*administration & dosage/adverse effects MH - Antineoplastic Combined Chemotherapy Protocols/administration & dosage MH - Breast Neoplasms/*drug therapy/*metabolism MH - Chemotherapy, Adjuvant MH - Dose-Response Relationship, Drug MH - Drug Resistance, Neoplasm/drug effects MH - Epothilones/*administration & dosage/adverse effects MH - Female MH - Humans MH - Middle Aged MH - Neoplasm Metastasis MH - Receptor, ErbB-2/*metabolism PMC - PMC4568133 MID - NIHMS684178 OTO - NOTNLM OT - Chemoresistance OT - Circulating tumor cells OT - Ixabepilone OT - Neoadjuvant systemic therapy OT - Residual disease EDAT- 2015/04/29 06:00 MHDA- 2016/06/21 06:00 PMCR- 2016/10/01 CRDT- 2015/04/28 06:00 PHST- 2014/10/13 00:00 [received] PHST- 2015/03/18 00:00 [accepted] PHST- 2015/04/28 06:00 [entrez] PHST- 2015/04/29 06:00 [pubmed] PHST- 2016/06/21 06:00 [medline] PHST- 2016/10/01 00:00 [pmc-release] AID - S1526-8209(15)00068-3 [pii] AID - 10.1016/j.clbc.2015.03.004 [doi] PST - ppublish SO - Clin Breast Cancer. 2015 Oct;15(5):325-31. doi: 10.1016/j.clbc.2015.03.004. Epub 2015 Mar 24.