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Evaluation of the effect of incidental beta blocker use on clinical response to the EGFR TKI, afatinib

Evaluation of the effect of incidental beta blocker use on clinical response to the EGFR TKI, afatinib

John Heymach, MD, PhD

MD Anderson Cancer Center

Self-funded, The University of Texas MD Anderson Cancer Center

No collaborations or engagements with sponsor companies that are tangentially related to this research proposal.

18 March 2015

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death. Epidermal growth factor receptor (EGFR) inhibitors such as afatinib are particularly effective in a subset of lung cancer patients. However, resistance inevitably occurs and remains a major hurdle. If this resistance could be better understood, therapies could be developed to target these pathways and in doing so improve outcomes.
Chronic stress, which is common in cancer patients, causes a rise in epinephrine and norepinephrine as well as “stress” receptors, termed adrenergic receptors. This process has also been shown to reduce survival in cancer patients, and to accelerate disease progression in mouse models. We have demonstrated that treatment of NSCLC cells with stress hormones renders them resistant to epidermal growth factor inhibitors such as afatinib. This effect can be attenuated with beta blockers.
Based on these findings, our current study assesses the relationship between beta blocker use and response to afatinib. We hypothesize that beta blocker use will delay resistance and improve response to drugs such as afatinib. In this proposal, we will compare clinical response to afatinib in patients who did or did not take beta blockers. Findings from this study have direct clinical implications as a number of specific, well tolerated, and relatively inexpensive beta blockers are clinically available.

[{ "PostingID": 2382, "Title": "BI-1200.32", "Description": "BIBW 2992 (Afatinib) Versus Chemotherapy as First Line Treatment in NSCLC With EGFR Mutation

Medicine: afatinib , Condition: Carcinoma, Non-Small-Cell Lung; Adenocarcinoma, Phase: 3, Clinical Study ID: 1200.32, Sponsor: Boehringer Ingelheim" }]

Statistical Analysis Plan