DDDR-19. PHARMACOSCOPY FOR BRAIN METASTASES FROM NON-SMALL CELL LUNG CANCER (NSCLC)

Abstract 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. Here we performed an explorative feasibility study to profile ex vivo drug sensitivities across a large panel of classical anti-cancer as well as neuroactive drugs, using an automated imaging platform called “pharmacoscopy”. The anti-cancer drug panel included chemotherapies and targeted therapies such as receptor tyrosine kinase, cyclin dependent kinase, and BCL2 inhibitors. The neuroactive drug panel included antidepressants and antipsychotics. A total of 19 samples from 17 patients were dissociated after surgery and incubated with drugs for 48 hours ex vivo to measure drug sensitivities. Patient cancer cells were identified by immunofluorescence using EpCAM, TTF-1, or CK7 as markers whereas immune cells were identified by CD45. On-target drug activity (pharmacoscopy score) was measured by quantifying the specific reduction of cancer cells upon drug treatment. Among the top ranking drugs ex vivo, several patient samples displayed on-target responses to candidate targeted therapies such as the CDK4/6 inhibitor abemaciclib, the BCL2 inhibitor venetoclax, and the MEK inhibitor cobimetinib as well as unexpected sensitivies to certain neuroactive drugs. Integration of pharmacoscopy results with molecular data from next generation sequencing in the respective brain metastases tissues is ongoing. 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.