Phase Ib Trial Of Trastuzumab Emtansine (Te) In Combination With Lapatinib (L) Plus Nab-Paclitaxel (A) In Metastatic Her2-Neu Overexpressed Breast Cancer Patients: Stela Trial Results

Background: Multiple large randomized clinical trials have demonstrated that dual HER2 targeted therapies are synergistic and result in improved efficacy. We conducted a phase Ib trial of trastuzumab-emtansine (TE) and lapatinib (L), together with Nab paclitaxel (A) in patients with HER2 over-expressed stage IV breast cancer. Methods: Key inclusion criteria are stage IV HER2 positive breast cancer, LVEF ≥ 45%, and Peripheral neuropathy Results: Nine patients, median age 47 (range 44-64) years were enrolled. All patients are currently off the study. The DLTs were grade 3 diarrhea (n = 1) and grade 3 elevated transaminase (n = 1). Grade 3-4 hematological toxicities included neutropenia (N = 6) and thrombocytopenia (N = 1). Other AEs included grade 1-2 mucositis (n = 2), diarrhea (N = 2), and liver function tests abnormality (N = 5). The 24 hour trough levels of each of the drug were within the range of the values reported in the literature. The MTD of TE, L and A was reached at: TE 3.0 mg/kg, Lapatinib 750mg and Abraxane (A) 80 mg/m2. Eight patients, with a median of 1 prior metastatic therapy (range 0-5) were evaluable for response. Five patients, 62.5% derived clinical benefit, including 1 patient with complete response and 4 patients with partial response. Conclusions: TE plus L and A therapy was well tolerated with antitumor activity observed. STELA Ib trial has been expanded to include twelve additional patients for safety and efficacy evaluation. Citation Format: Tejal Patel, Jaime Mejia, Angel Rodriguez, Jenny Chang. Phase Ib trial of trastuzumab emtansine (TE) in combination with lapatinib (L) plus nab-paclitaxel (A) in metastatic HER2-neu overexpressed breast cancer patients: STELA trial results. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT304. doi:10.1158/1538-7445.AM2015-CT304