A phase II trial of ixabepilone and cyclophosphamide as neoadjuvant therapy for patients with HER2-negative breast cancer: correlation of pathologic complete response with the 21-gene recurrence score.
Ixabepilone and the taxanes have similar activity in the first-line treatment of metastatic breast cancer, and ixabepilone is sometimes effective in taxane-refractory patients. We conducted a phase 2 trial to evaluate ixabepilone in combination with cyclophosphamide as neoadjuvant treatment for patients with locally advanced HER2-negative breast cancer. Response to neoadjuvant treatment was correlated with the baseline 21-gene Recurrence Score® (Oncotype DX; Genomic Health Inc, Redwood City, CA). Eligible women with HER2-negative locally advanced breast cancer received ixabepilone 40 mg/m(2) plus cyclophosphamide 600 mg/m(2) on day 1 of each 21-day cycle. Following 6 cycles, patients underwent definitive surgery. Primary endpoint was rate of pathologic complete response (pCR). Breast biopsy tumor samples were obtained at pretreatment and at surgery in patients with residual disease. Tumor specimens were analyzed using the 21-gene assay. One hundred sixty-eight patients (median age 52 years; 45 % triple-negative) were enrolled; 161 (96 %) underwent definitive surgery following neoadjuvant ixabepilone/cyclophosphamide. Overall, 27 patients (17 %) achieved pCR, including 19 of 73 (26 %) triple-negative patients. The most frequently occurring grade 3/4 toxicity was neutropenia (98 patients; 58 %). Recurrence Scores were highly correlated with achievement of pCR (0/36 with low or intermediate Recurrence Scores vs. 19/72 with high Recurrence Scores; p = 0.002). There was high concordance between baseline and post-treatment Recurrence Scores in the 72 patients with paired samples. The combination of ixabepilone and cyclophosphamide yielded a pCR rate of 17 %, similar to other neoadjuvant chemotherapy regimens. Pathologic complete responses occurred only in patients with high-risk baseline Recurrence Scores.
Sarah Cannon Research Institute, 3322 West End Ave., Suite 900, Nashville, TN, 37203, USA. dyardley@tnonc.com.|Tennessee Oncology, PLLC, Nashville, TN, USA. dyardley@tnonc.com.
Denise A
DA
Yardley
Sarah Cannon Research Institute, 3322 West End Ave., Suite 900, Nashville, TN, 37203, USA.|Tennessee Oncology, PLLC, Nashville, TN, USA.
Nancy W
NW
Peacock
Sarah Cannon Research Institute, 3322 West End Ave., Suite 900, Nashville, TN, 37203, USA.
Mythili
M
Shastry
Sarah Cannon Research Institute, 3322 West End Ave., Suite 900, Nashville, TN, 37203, USA.|Tennessee Oncology, PLLC, Nashville, TN, USA.
Howard A
HA
Burris
Oncology Hematology Care, Inc, Cincinnati, OH, USA.
Rebecca G
RG
Bechhold
Center for Breast Health, Bethesda, MD, USA.
Carolyn B
CB
Hendricks
Genomic Health, Inc, Redwood City, CA, USA.
Carl N
CN
Yoshizawa
Genomic Health, Inc, Redwood City, CA, USA.
Amy P
AP
Sing
Sarah Cannon Research Institute, 3322 West End Ave., Suite 900, Nashville, TN, 37203, USA. john.hainsworth@scresearch.net.|Tennessee Oncology, PLLC, Nashville, TN, USA. john.hainsworth@scresearch.net.
John D
JD
Hainsworth
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D034261:Epothilones / Q000008:administration & dosage; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D003520:Cyclophosphamide; D034261:Epothilones; D018719:Erb-b2 Receptor Tyrosine Kinases; C430592:ixabepilone
21-gene Recurrence Score; Cyclophosphamide; HER2-negative breast cancer; Ixabepilone; Neoadjuvant; Oncotype DX