Abstract P5-17-05: Sorafenib plus Ixabepilone as First-Line Treatment for Patients with HER2-Negative Metastatic Breast Cancer: Preliminary Results of the Phase II Trial of the Sarah Cannon Research Institute
Authors: Yardley DA , Barton J , Dickson N , Shipley D , Drosick DR , Hendricks C , Inhorn RC , Shastry M , Finney L , Burris HA 
Published: August 2014

Abstract
Background: Sorafenib (S) is an oral multi-kinase inhibitor with effects on tumor proliferation and angiogenesis, targeting VEGFR1 and VEGFR2. It has modest activity as a single agent in breast cancer. In combination with capecitabine, S demonstrated a significant improvement of 2.3 months in progression free survival (PFS) in patients (pts) with metastatic breast cancer (MBC) and added benefit when combined with paclitaxel. Ixabepilone (Ixa) is a semi-synthetic analog of epothilone B with excellent single agent activity in MBC. The phase I portion of this trial identified the MTD of the Ixa and S combination. We now report the initial results of the phase II trial with this novel combination.
Methods: Eligibility criteria included: HER2-negative MBC previously untreated with chemotherapy; measurable disease; ECOG PS 0–2; normal LVEF; and adequate bone marrow and organ function. Prior hormonal therapy for MBC was permitted. Pts received Ixa 32mg/m2 IV on day 1 of each 21-day cycle and S 400mg PO BID. Following a minimum of 4 cycles of the combination, responding pts could discontinue Ixa and remain on study treatment with S monotherapy. Granulocyte-stimulating growth factors were permitted after cycle one. Tumor assessments were performed every 9 weeks. Pts continued study treatment until disease progression or unacceptable toxicity. The primary endpoint of this trial was PFS; the addition of S to Ixa was hypothesized to improve PFS from 4.2 month to 6.2 months in this patient population. The total enrollment goal is 85 pts, and the trial is currently open to accrual.
Results: Between 5/2010 and 4/2012, 76 pts have been enrolled, and 57 pts (56 females, 1 male) are included in this analysis. Baseline characteristics included: median age 58; 61% were ER and/or PR positive; 39% were triple-negative; 39% received neoadjuvant therapy. Anthracycline exposure was noted in 34 pts and prior taxane exposure in 39 pts. 29 pts received prior hormonal therapy, 7 of these for MBC. Sites of metastatic disease included lymph nodes 42%, lung 35%, liver 30%, bone 30%, and 23% other. 19 pts (33%) had 3 or more sites of metastatic disease. Median treatment duration was 3 cycles (9 weeks), range 1–11+ cycles with 9 pts discontinuing Ixa after a median of 6 cycles and continuing on S monotherapy. 12 pts (21%) had objective responses (1 CR, 11 PR); 3 of the 22 (14%) triple-negative patients had responses (1 CR, 2 PR). An additional 24 patients (42%) had stable disease at first reevaluation. Neutropenia was the most common grade 3/4 toxicity (26%) with growth factor use reported in 35%. Grade 3/4 non-hematologic toxicity occurring in &gt; 5% of patients consisted of: rash (12%), fatigue (11%), hypersensitivity reaction (7%, Ixa= 3 pts and S= 1 pt), and neuropathy (7%). Discontinuation due to adverse events occurred in 11%.
Conclusion: The combination of Ixa and full dose S was well tolerated with no new observed toxicities. Adverse events were manageable and consisted primarily of G3/4 neutropenia and rash. Study is ongoing and updated results will be presented.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-17-05.