Phase II Randomized Study of Ixabepilone Versus Observation in Patients With Significant Residual Disease After Neoadjuvant Systemic Therapy for HER2-Negative Breast Cancer.
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.
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.
Ana M
AM
Gonzalez-Angulo
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX.
Xiudong
X
Lei
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
Richardo H
RH
Alvarez
Genentech, South San Francisco, CA.
Majorie C
MC
Green
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
James L
JL
Murray
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
Vicente
V
Valero
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
Kimberly B
KB
Koenig
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
Nuhad K
NK
Ibrahim
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
Jennifer K
JK
Litton
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
Lakshmy
L
Nair
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX.
Savitri
S
Krishnamurthy
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
Gabriel N
GN
Hortobagyi
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.
Funda
F
Meric-Bernstam
D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D034261:Epothilones / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*
D000970:Antineoplastic Agents; D034261:Epothilones; D018719:Erb-b2 Receptor Tyrosine Kinases; C430592:ixabepilone
Chemoresistance; Circulating tumor cells; Ixabepilone; Neoadjuvant systemic therapy; Residual disease