110P - Biomarkers for afatinib and dasatinib treatment in triple negative breast cancer
Date | 10 October 2016 |
Event | ESMO 2016 Congress |
Session | Poster display |
Topics | Breast Cancer Translational Research Basic Principles in the Management and Treatment (of cancer) |
Presenter | Alexandra Canonici |
Citation | Annals of Oncology (2016) 27 (6): 15-42. 10.1093/annonc/mdw363 |
Authors |
A. Canonici1, M.F..K. Ibrahim1, K. Fanning1, M. Cremona2, C. Morgan2, B. Hennessy2, F. Solca3, J. Crown4, N. O'Donovan1
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Abstract
Background
Triple negative breast cancer (TNBC) lacks expression of hormone receptors and amplification of HER2. There are currently no approved targeted therapies. EGFR is frequently overexpressed in TNBC and may be a rationale target. The activity of afatinib, an irreversible pan-HER TKI, was assessed alone and in combination with inhibitors of other promising targets for TNBC.
Methods
Sensitivity to afatinib and other targeted therapies was assessed using proliferation assays. IC50 and CI values were determined using CalcuSyn. Statistical analyses were performed on StatView software. Proteomic profiling was performed by Reverse Phase Protein Array (RPPA).
Results
As previously shown (Ibrahim et al, ASCO 2014), the IC50 values for afatinib in 14 TNBC cell lines ranged from 0.007-5.0 µM. 3 of the 7 basal-like cell lines were sensitive to afatinib (IC50
Conclusions
Afatinib in combination with dasatinib may have activity in TNBC. Bcl2 may be a predictive biomarker to identify patients who are more likely to benefit from this combination. RPPA results suggest that efficient inhibition of both ERK and Akt signalling may contribute to the synergistic anti-proliferative effects of afatinib combined with dasatinib.
Clinical trial identification
Legal entity responsible for the study
Dublin City University
Funding
Boehringer Ingelheim
Disclosure
A. Canonici, N. O'Donovan: Received research funding from Boehringer Ingelheim. F. Solca: Eployee of Boehringer Ingelheim. J. Crown: Received research funding from Boehringer Ingelheim; and travel, accommodation and expenses from Bristol-Myers Squibb. All other authors have declared no conflicts of interest.