IV NSCLC (original) (raw)

Annals of Oncology, 2012

Abstract

ABSTRACT Background Inhibition of Hsp90, a key molecular chaperone required for activation of many oncoproteins, can lead to cancer cell death. Ganetespib (G) is an Hsp90 inhibitor that has shown single agent activity in molecularly defined disease, including ELM4-ALK rearrangement, KRAS mutations, HER2 amplification and BRAF mutations. Circulating free DNA (cfDNA) is present at low levels in plasma of healthy individuals, whereas its increased concentration was observed in patients with malignant tumors including non-small cell lung cancer (NSCLC). Cancer gene somatic mutations can be detected in cfDNA. Methods This is a randomized trial, comparing G+ docetaxel (D), to D in 2nd line advanced NSCLC patients. This study aimed at investigating the potential usefulness of plasma DNA concentration in NSCLC patients for efficacy of therapy. We performed a prospective exploratory analysis to identify serum biomarkers as predictors of improved outcomes with G. Plasma samples were collected from 160 pts at baseline prior to initiation of treatment, and at end of cycles 1 and 2. cfDNA was evaluated using the Ion Torrent platform to survey mutations in 46 cancer genes. Serum levels were correlated with progression free survival (PFS) and overall survival (OS) in both treatment arms. Upfront enrichment using both nanoparticle capture and phosphoprotein capture technologies were coupled to high resolution Orbitrap-LTQ MS/MS analysis followed by spectral counting for each samples. Results By early May approximately half of the 300 planned patients were enrolled. Baseline characteristics were balanced. Full proteomic profiling and cfDNA analysis is ongoing, and will be correlated with the efficacy outcomes from a planned interim analysis in early September, including disease control rate, PFS, and OS. Disclosure I. El Hariry: stock ownership. V. Vukovic: stock ownership. F. Teofilovici: stock option. V. Reichert: stock options. All other authors have declared no conflicts of interest.

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