Abstract Background: We conducted a multicenter, randomized open-label phase II neoadjuvant study of trastuzumab-emtansine (T-DM1), Lapatinib (L) and Nab Paclitaxel (Nab-P) compared to 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 a biologic window of targeted therapies alone for 6 weeks (T-DM1 and L) followed by 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 targeted therapies alone for 6 weeks (T and P) followed by Pac 80mg/m2QW, 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 which are being reported. Results: Thirty of the 33 enrolled patients were evaluable. Patient demographics were well balanced. HER2 subtypes and altered PIK3CA (low PTEN or PIK3CA mutations) pathway were not statistically different between both arms. We have previously reported that all patients achieved RCB 0 & I in the T-DM1, L and Nab-P arm, compared to SOC (100% vs. 62.5%, p 0.0035). In the SOC arm, the 6 week change in tumor size on breast MRI during targeted biologic window treatment is significantly different between the responders and non-responders based on two-sided Wilcoxon rank-sum test (p =0.0065). Consistent with literature, among ER positive patients treated with SOC, PTEN low expressers were less likely to respond (0%, 0 of 2) than PTEN high expressers (67%, 2 of 3). In the experimental arm, all patients responded regardless of PTEN. There was only 1 PIK3CA mutation on the experimental arm where all responded. Table 1:Breast MRI Tumor Size Standard of Care ArmResponseNMeanStandard Deviation95% CL MeanMinimumMaximumNo6-0.13330.4457-0.60110.3344-1.00.3Yes52.58001.88330.24154.91850.24.9Sixteen patients total were present in standard of care arm but 5 had incomplete imaging data. Conclusions: TDM1 plus L and Nab-P therapy was well tolerated with noteworthy responses in all patients, including in PTEN low expressers. Change in tumor size at 6 weeks of biologic therapies was significant between responders and non-responders and can be evaluated as a surrogate for future studies. Citation Format: Creamer SL, Patel TA, Ensor JE, Rodriguez AA, Niravath PA, Darcourt JG, Kaklamani VG, Meisel JL, Li X, Zhao J, Kuhn JG, Rosato RR, Qian W, Belcheva A, Boone T, Chang J. Care 001: multi-center randomized open-label phase II trial of neoadjuvant trastuzumab emtansine (T-DM1) in combination with lapatinib and nab-paclitaxel compared with paclitaxel, trastuzumab and pertuzumab in HER2-neu over-expressed breast cancer patients (TEAL study) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-17-26.
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