Dual targeting of HER2-positive breast cancer with trastuzumab emtansine and pertuzumab: understanding clinical trial results
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Alberto Ocaña1, Eitan Amir2 and Atanasio Pandiella3
1Translational Research Unit, Albacete University Hospital, and CIBERONC, Albacete, Spain
2Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada
3Cancer Research Center, CSIC-IBSAL and CIBERONC, Salamanca, Spain
Alberto Ocaña, email: [email protected]
Keywords: breast cancer; HER2; trastuzumab; pertuzumab; TDM1
Received: May 15, 2018 Accepted: June 23, 2018 Published: August 07, 2018
Targeting of HER2-positive tumors with trastuzumab has shown to improve survival in early stage and advanced breast cancer. The addition of pertuzumab, another anti-HER2 antibody, to trastuzumab-containing regimens has demonstrated a modest increase in disease-free survival in the adjuvant setting. Unexpectedly, when pertuzumab was explored in combination with the antibody-drug conjugate TDM1 in the metastatic setting, no additional benefit was observed compared with dual targeting of HER2 with pertuzumab and trastuzumab, together with chemotherapy. Similar results were observed when exploring pathologic complete response in the neoadjuvant setting. In this article, we discuss basic science and translational data that may explain the limited efficacy observed with the combination of TDM1 and pertuzumab, including tumor heterogeneity, clonal selection, bystander effect or downregulation of the receptor by competitive binding. In addition, we review ongoing studies that could help to understand these findings.
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