P5-13-09: Correlation of Oncotype DX Recurrence Scores with Pathologic Response Following Neoadjuvant Ixabepilone and Cyclophosphamide in Patients with HER2−Negative Breast Cancer: A Sarah Cannon Research Institute Phase II Trial.
Authors: Yardley DA , Peacock NW , Hendricks C , Huh SY , Ketchum S , Chao C , Yoshizawa C , Burris III HA , Hainsworth JD 
Published: June 2012

Abstract
Background: Ixabepilone (Ixa) is active in anthracycline and taxane-refractory metastatic breast cancer as well as in the neoadjuvant setting where Ixa yielded a pathologic complete response (pCR) rate of 11%. In this study, we evaluated Ixa in combination with cyclophosphamide (C) as neoadjuvant treatment for ER+/ER- HER2−negative breast cancer. The primary endpoint was pathologic complete response (pCR) rate, defined as no residual invasive cancer in breast or lymph nodes. The Oncotype DX Breast Cancer Assay, that uses reverse transcriptase-polymerase chain reaction (RT-PCR) to assess a panel of 21 tumor genes to calculate a score predictive of the likelihood of the magnitude of adjuvant chemotherapy benefit, was applied to pretreatment and residual disease tumor samples obtained at the time of definitive surgery. The likelihood of whether neoadjuvant clinical or pathological responses may be predicted by Oncotype DX recurrence scores (RS®) was assessed. An interim analysis of the first 81 patients (pts) was reported at ASCO 2011. The final analysis will be presented on all 168 pts.
Methods: Eligible women had locally advanced breast cancer that was HER2−negative (IHC 0–1+ or FISH negative), T &gt;2 cm or lymph node positive. Pts with inflammatory breast cancer or T1N0 tumors were excluded. Pts received Ixa 40mg/m2 with C 600mg/m2 day 1 q21 days x6 cycles. Following 6 cycles, had definitive surgery. Postoperative locoregional radiation therapy and/or hormonal treatments were at discretion of the treating MD per institutional guidelines. Breast core biopsy tumor samples were obtained pretreatment and at the time of surgery in those pts demonstrating residual disease at surgery. Tumor specimens were analyzed using the Oncotype DX RT-PCR assay. An interim pretreatment RS assessment in the first 38 pts and paired samples in 21 pts was conducted and correlated with clinical and pathologic responses.
Results: 168 women enrolled. Baseline characteristics and toxicity for the first 118 pts are reported (median age 52 years; 90% invasive ductal carcinoma; T2/T3 52%/31%; 42% triple negative). 81 pts have undergone surgery. 25 pts discontinued treatment early (toxicity — 12; disease progression — 8; pt/MD request — 3; pt non-compliance — 2).Grade 3/4 toxicity included: neutropenia (65%), leukopenia (47%), neuropathy (10%), and febrile neutropenia (7%). Preliminary toxicity results with this neoadjuvant treatment have been previously reported (Peacock et al, ASCO 2011 Abstract #1066). Oncotype DX pretreatment evaluations for the initial 38 pts demonstrated a significant logistic regression of pretreatment recurrence score with pCR (p = 0.025).
Conclusions: Neoadjuvant therapy with Ixa and cyclophosphamide yielded a preliminary pCR rate of 19% (in 81 pts), similar to results with other 2-drug combination chemotherapy regimens. Preliminary Oncotype DX assessments at baseline indicated that baseline recurrence scores may predict pCR rates. These exploratory Oncotype DX recurrence scores at baseline and paired with scores obtained at the surgery and correlations with pCR will be presented for the entire cohort.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-13-09.