María Teresa Martínez1, José Alejandro Pérez-Fidalgo2, Paloma Martín-Martorell2, Juan Miguel Cejalvo2, Vanesa Pons2, Begoña Bermejo2, Miguel Martín3, Joan Albanell4, Ana Lluch5. 1. Dept. of Hematology and Medical Oncology, Biomedical Research Institute INCLIVA, University of Valencia, "Rio Hortega Project in research training" (CM12/00264), Spain. Electronic address: maitemartinez3@yahoo.es. 2. Dept. of Hematology and Medical Oncology, Biomedical Research Institute INCLIVA, University of Valencia, Spain. 3. Dept. of Medical Oncology, Hospital General Universitario Gregorio Marañón, Madrid, Spain. 4. Dept. of Medical Oncology, Hospital Del Mar, Barcelona, Spain. 5. Dept. of Hematology and Medical Oncology, Biomedical Research Institute INCLIVA, University of Valencia, Spain. Electronic address: lluch_ana@gva.es.
Abstract
BACKGROUND: Trastuzumab emtansine (T-DM1), a new agent developed for the treatment of HER2-positive breast cancer, is an antibody-drug conjugate with a complex compound obtained by the conjugation of trastuzumab, a stable thioether linker, and the potent cytotoxic drug maytansine-derivate(DM1), which inhibits cell division and induces cell death. FIELD OF STUDY: PubMed database, ESMO, ASCO, San Antonio Breast Cancer Symposium Meeting abstracts and clinicaltrials.gov were searched using the terms "Anti-HER2 treatment breast cancer and trastuzumab emtansine (T-DM1) "; papers considered relevant for the aim of this review were selected. FINDINGS/ RESULTS: The phase I trials have determined the safe dosing range of T-DM1, established at 3.6 mg/kg every 3 weeks. The phase III randomized EMILIA and TR3RESA trials have shown that T-DM1 provides objective tumor responses and significantly improves progression free survival and overall survival in HER2-positive metastatic breast cancer patients previously treated with anti-HER2-based regimens. The ongoing phase III trials KAITLIN and KATHERINE will give us further information about the place T-DM1 should occupy in the treatment of patients with early stage HER2-positive breast cancer. In this review we analyze the most relevant clinical trials conducted with T-DM1 and the role of this compound in the management of advanced breast cancer. CONCLUSION: T-DM1 has shown clinically relevant activity in the treatment of HER2-positive breast cancer patients after progression on trastuzumab and taxane based therapy, both in the second line treatment setting and after early relapse on adjuvant trastuzumab therapy. This is accompanied by a favorable safety and tolerability profile.
BACKGROUND:Trastuzumab emtansine (T-DM1), a new agent developed for the treatment of HER2-positive breast cancer, is an antibody-drug conjugate with a complex compound obtained by the conjugation of trastuzumab, a stable thioether linker, and the potent cytotoxic drug maytansine-derivate(DM1), which inhibits cell division and induces cell death. FIELD OF STUDY: PubMed database, ESMO, ASCO, San Antonio Breast Cancer Symposium Meeting abstracts and clinicaltrials.gov were searched using the terms "Anti-HER2 treatment breast cancer and trastuzumab emtansine (T-DM1) "; papers considered relevant for the aim of this review were selected. FINDINGS/ RESULTS: The phase I trials have determined the safe dosing range of T-DM1, established at 3.6 mg/kg every 3 weeks. The phase III randomized EMILIA and TR3RESA trials have shown that T-DM1 provides objective tumor responses and significantly improves progression free survival and overall survival in HER2-positive metastatic breast cancerpatients previously treated with anti-HER2-based regimens. The ongoing phase III trials KAITLIN and KATHERINE will give us further information about the place T-DM1 should occupy in the treatment of patients with early stage HER2-positive breast cancer. In this review we analyze the most relevant clinical trials conducted with T-DM1 and the role of this compound in the management of advanced breast cancer. CONCLUSION: T-DM1 has shown clinically relevant activity in the treatment of HER2-positive breast cancerpatients after progression on trastuzumab and taxane based therapy, both in the second line treatment setting and after early relapse on adjuvant trastuzumab therapy. This is accompanied by a favorable safety and tolerability profile.