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

Abstract

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-naïve 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%) for an ORR = 18/26 (69%) and CBR = 24/26 (92.3%). Selected EVBR were CDDP/gemcitabine 12/26 (46%); CDDP/taxane 7/26 (27%); erlotinib 5/26 (19%); CDDP/vinorelbine 1/26 (4%); CDDP/pemetrexed1/25 (4%). Nine of 26 (36.6%) pts were converted to surgical/radiation candidates. All first-line erlotinib pts responded (100%). Conclusions: At ORR = 69%, the trial has met response criteria and with current TTP up to 46 months and OS up to 60 months, accrual will be completed to allow formal TTP and OS analyses. The EVA/PCD platform, by examining drug-induced events in native-state micro-spheroids, has shown the unique capacity to capture stromal, vascular and inflammatory cell interactions with tumor cells, known crucial for clinical response prediction. Results support applications of personalized NSCLC therapy and warrant further evaluation. Supported by Memorial Medical Center Foundation, Long Beach. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Rational Therapeutics Rational Therapeutics