Phase II trial of personalized chemotherapy in stage IV NSCLC: Clinical application of functional profiling in first-line therapy.

7617 Background: Personalized chemotherapy is an important advance for NSCLC pts. While genomic platforms have identified prognostic and predictive factors e.g., ERCC1 and RRM1/2, proteomic platforms are now identifying novel phosphoprotein targets. To address the complexity and redundancy of cell-death pathways, we applied Ex Vivo Analysis of Programmed Cell Death (EVA/PCD) (Nagourney, R. Curr Treat Opt Oncol. 2006) to select therapy for chemo-naive pts with stage IV NSCLC. Methods: Using morphologic and metabolic endpoints EVA/PCD gauges cellular response to drugs and signal transduction inhibitors in human tumor micro-spheroids isolated from surgical biopsies. Modified Z-scores and synergy analyses (median-effect) then select ex vivo best regimens (EVBR) from FDA-approved NSCLC drugs. Trial powered to improve ORR by 2-fold and median TTP by 50% (p=.05). All pts sign informed consent. Results: 26/32 (81%) pts are evaluable with CR = 3/26 (11.5%); PR = 15/26 (57.6%); SD = 6/26 (23%) and PD = 2/26 (7.6%) ...