Abstract ES9-1: Adjuvant Treatment of HER2 Positive Breast Cancer: The Next Installment
Authors: Pietenpol JA 
Published: August 2014

Abstract
The treatment of HER2 positive breast cancer radically changed in 2005; at ASCO that year adjuvant trials reported that the addition of trastuzumab consistently showed a major improvement in progression free survival in the treatment of early breast cancer that was HER2 positive. A benefit was seen when trastuzumab was given either concurrently with chemotherapy or sequentially. The trials generally studied one year of trastuzumab although data from Finland showed a benefit for 3 months of treatment. Additional, yet to be reported studies, have explored durations of 6 months and 2 years. Initially there was concern about cardio toxicity and the potential for significant long-term harm, but the rate of cardio toxicity remains low and usually is seen early in the treatment. To further improve outcomes, new agents have been studied in the neo and adjuvant settings. The large ALTTO study randomized patients to either chemotherapy with either a year of trastuzumab, a year of lapatinib (the TKI inhibitor with efficacy in the metastatic arena), the combination of both agents or sequential use of each agent. The lapatinib monotherapy arm was shown to be inferior in an interim analysis and discontinued. Final data is pending although extrapolating from the NEOALTTO study, one may expect heightened activity from dual blockade. The BETH study added bevacizumab to trastuzumab in a 2-arm study trying to combat angiogenesis with HER2 blockade; this study has not reported. Although the same combination studied in the AVEREL study in the advanced setting did not show a benefit, this may not be the case in earlier disease and we need to wait for data. Dual blockade with two antiHER2 agents has been beneficial in the advanced setting and this has led to the APHINITY study, which is comparing chemotherapy with standard trastuzumab or trastuzumab with another antiHER2 antibody, pertuzumab. This study is accruing well and will provide evidence for whether dual blockade with two antibodies is of benefit. It will also provide some clinical trial data for small tumors, as these are eligible for enrollment in this trial. Other new agents, including TDM 1, are being taken into the neoadjuvant setting and will be in adjuvant trials soon. Subcutaneous trastuzumab may provide easier treatment for women over their year of adjuvant therapy. A big question is whether all HER2 tumors are the same or whether we can begin tailoring treatment according to molecular features. Are there some cancers that will be cured with a short course of chemotherapy and trastuzumab while others may need multiple antiHER2 agents combined to acquire the same result? With the collection of tumor samples we can hopefully begin to further understand this. Tailored treatment has the potential to decrease toxicity and improve quality of life issues, provide more rational use of costly resources, and finally develop more intensive therapy for resistant tumors thus improving outcomes overall.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr ES9-1.