TY - JOUR
T1 - Phase II Randomized Study of Ixabepilone Versus Observation in Patients with Significant Residual Disease after Neoadjuvant Systemic Therapy for HER2-Negative Breast Cancer
AU - Gonzalez-Angulo, Ana M.
AU - Lei, Xiudong
AU - Alvarez, Richardo H.
AU - Green, Majorie C.
AU - Murray, James L.
AU - Valero, Vicente
AU - Koenig, Kimberly B.
AU - Ibrahim, Nuhad K.
AU - Litton, Jennifer K.
AU - Nair, Lakshmy
AU - Krishnamurthy, Savitri
AU - Hortobagyi, Gabriel N.
AU - Meric-Bernstam, Funda
N1 - Funding Information:
This work was supported in part by Komen for the Cure Catalytic Award KG090341 (AMG-A), Komen for the Cure Grant SAC 100004 (AMG-A), American Cancer Society Research Scholar Grant 121329-RSG-11-187-01-TBG (AMG-A), The Commonwealth Foundation for Cancer Research (AMG-A), and Bristol-Myers Squibb (New York, NY) .
Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.
PY - 2015/10/1
Y1 - 2015/10/1
N2 - 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.
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.
KW - Chemoresistance
KW - Circulating tumor cells
KW - Ixabepilone
KW - Neoadjuvant systemic therapy
KW - Residual disease
UR - http://www.scopus.com/inward/record.url?scp=84941314879&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84941314879&partnerID=8YFLogxK
U2 - 10.1016/j.clbc.2015.03.004
DO - 10.1016/j.clbc.2015.03.004
M3 - Article
C2 - 25913905
AN - SCOPUS:84941314879
SN - 1526-8209
VL - 15
SP - 325
EP - 331
JO - Clinical breast cancer
JF - Clinical breast cancer
IS - 5
ER -