Care 001: Multicenter randomized open label phase II trial of neoadjuvant trastuzumabemtansine (T-DM1) in combination with lapatinib and nab-paclitaxel compared with paclitaxel, trastuzumab and pertuzumab in HER 2 neu over-expressed breast cancer patients (TEAL study).

581 Background: Based on data from our phase I study of trastuzumab-emtansine (T-DM1), Lapatinib (L) and Nab Paclitaxel (Nab-P), a multicenter randomized open label phase II neoadjuvant study was conducted comparing this regimen to the standard of care (SOC) Paclitaxel (Pac), Trastuzumab (T), and Pertuzumab (P) in patients with HER2 over-expressed breast cancer. Methods: Patients in the experimental arm received T-DM1 3.0 mg/kg Q3W, L 750mg oral daily and Nab-P 80 mg/m2 weekly (QW) X 12 weeks. Patients in SOC arm received Pac 80mg/m2 QW, T 2mg/kg QW, and P 420mg Q3W X 12 weeks. The primary objective was to evaluate the proportion of patients with residual cancer burden (RCB) 0 or 1. Key secondary objectives included correlative assessments of PIK3CA mutations, PTEN expression, and HER2 subtypes, all of which are ongoing. Results: Thirty of the 33 enrolled patients were evaluable. Patient demographics were.The proportion of patients with RCB 0 & I was significantly higher in the T-DM1, L and Nab-P arm than in the SOC arm (100% vs. 62.5%, p 0.0035). Importantly, the RCB 0 & 1 in the ER positive subset of patients was 100% compared with 25% in SOC (p 0.0035). Common adverse events included elevated liver function tests, fatigue, diarrhea and neuropathy. Conclusions: TDM1 plus L and Nab-P therapy was well tolerated with noteworthy responses in all patients, and especially in the ER positive subset, a group which has historically had lower response rates to neoadjuvant anti-HER2-directed therapy. Further evaluation of this regimen is warranted. Clinical trial information: NCT02073487.Efficacy. Experimental SOC P-value RCB 0 - and I 14 (100) 10 (62.5) 0.0035 ER Negative 6 (100) 8 (100) ER Positive 8 (100) 2 (25) RCB II and III 0 6 (37.50)