Preliminary Safety Results From A Multicenter Phase Ii Trial Of Nanoparticle Albumin-Bound Paclitaxel/Cyclophosphamide In Early Stage Breast Cancer Plus Trastuzumab In Her-2+Patients (Pts)

e11509 Background: Docetaxel/cyclophosphamide has demonstrated superior disease free and overall survival compared to doxorubicin/cyclophosphamide in the treatment of early stage breast cancer with an acceptable safety profile, with grade (G) 3/4 neutropenia of 61% and no cardiotoxicity. Nanoparticle albumin-bound (nabtm)-paclitaxel (nab-P) is a novel formulation with demonstrated superior efficacy to conventional paclitaxel (P) in treatment of metastatic breast cancer with a comparable safety profile. We therefore conducted a multicenter phase II pilot trial of weekly nab-P/cyclophosphamide to assess the safety and tolerability of this combination in early stage breast cancer. Methods: Eligibility: T1–4pN0–3M0, ECOG PS 0–2, normal organ function, normal LVEF for pts receiving trastuzumab (T). Treatment consisted of nab-P 100 mg/m2 day (D) 1, 8, 15 with cyclophosphamide (C) 600 mg/m2 D1 q 21 days x 4 cycles. T was given in IHC 3+ or FISH HER2+ pts with an 8 mg/kg loading dose followed by 6mg/kg q21D x 52 weeks. Results: 63 pts enrolled from April 2008 through September 2008; 33 pts are evaluable for safety with a median of 2 cycles. Baseline characteristics: median age 57 years (range 33–76); ECOG PS 0–94%, T1-T2 tumors - 100%, node negative 61%, hormone receptor negative 33%, HER 2+ 15%, triple negative 27%, ductal histology 73%, premenopausal 37 %. nab-P dose modifications occurred in 10 of 33 pts with nab-P reductions in 2 pts: 1 each due to G3 neutropenia- cycle 2 and G3 neuropathy- cycle 4. All 8 nab-P treatment delays were due to G3 neutropenia at D15. G3/4 neutropenia was present in 30% with only 1 G4 episode. 1 pt utilized myeloid colony stimulating factors. There were no G3/4 non-heme toxicities present in > 5 % of pts and no LVEF declines in pts receiving T. 17 pts remain on study with 3 pts receiving T. Conclusions: The combination of weekly nab-P with cyclophosphamide is feasible and well tolerated with an acceptable safety profile as adjuvant therapy for early stage breast cancer. The addition of T to this combination did not create any safety concerns. Full safety data for the 63 pts will be updated at the time of the meeting. [Table: see text]