TRLS-07 EX VIVO DRUG SENSITIVITY PROFILING (PHARMACOSCOPY) FOR BRAIN METASTASES FROM NON-SMALL CELL LUNG CANCER (NSCLC)

Abstract BACKGROUND Brain metastases remain a common and important complication in the course of disease in patients with non-small cell lung cancer (NSCLC). While targeted therapies and immunotherapies have led to prolonged disease control in subsets of patients with brain metastases from NSCLC, there is still an urgent need for novel treatments after failure of these standards and after exhaustion of local therapies including surgery and radiotherapy. METHODS We performed an explorative feasibility study to profile ex vivo drug sensitivities across a large panel of classical anti-cancer and neuroactive drugs, using an automated imaging platform called “pharmacoscopy”. The anti-cancer drug panel included chemotherapy and targeted therapy drugs such as receptor tyrosine kinase, cyclin-dependent kinase, and BCL2 inhibitors. The neuroactive drug panel included antidepressants and antipsychotics among others. 24 samples from 22 patients were incubated with drugs for 48 hours ex vivo to measure drug sensitivities. Cancer cells were identified by immunofluorescence using EpCAM, TTF-1, or CK7 as markers whereas immune cells were identified by CD45 expression. On-target drug activity (pharmacoscopy score) was measured by quantifying the specific reduction of cancer cells relative to non-neoplastic cells. RESULTS Among the top ranking drugs ex vivo, several patient samples displayed sensitivity to targeted therapies such as EGFR inhibitor osimertinib, CDK4/6 inhibitor abemaciclib, BCL2 inhibitor navitoclax, MEK inhibitor cobimetinib, as well as unexpected sensitives to certain neuroactive drugs including antidepressant sertraline. Tumors harboring EGFR mutations showed increased ex vivo drug sensitivity to a variety of drugs while tumors from patients receiving systemic treatment up to the point of surgery showed reduced sensitivity to the EGFR inhibitor, erlotinib. DISCUSSION Overall, this study demonstrates the feasibility of pharmacoscopy-based functional drug testing in NSCLC brain metastases, and highlights novel opportunities of personalized treatment for future exploratory clinical studies in patients with brain metastases from NSCLC.