Background:

Tumor heterogeneity is a key underlying factor that leads to resistance to chemo-and matched therapies. Circulating cell-free tumor DNA (ctDNA) may capture more tumor heterogeneity than a tissue biopsy-derived DNA analysis. In addition, markers of vasculogenesis have been shown to be sensitive markers of tumor growth vs. response to treatment. Here we study the impact of a novel multitargeted epigenetic therapy (MTET) on ctDNA, markers of vasculogenesis and radiographic response.

Methods:

One hundred consecutive patients with advanced solid tumor cancers were treated with multi targeted epigenetic therapy (MTET). More than 60% were stage IV, with 52% male and 48% women, 24 to 81 years of age. Pre-treatment and post-treatment imaging, circulatory tumour cells (CTC), (Biofocus Lab), ctDNA (Guardant Health, Inc.) and plasma VEGF (LabCorp) were obtained. PET scan metabolic activities were determined by a radiologist in a tertiary hospital based metabolic imaging canter. The average patient had undergone two or more lines of therapy previously. Patients underwent 10 or more cycles of a novel multitargeted epigenetic therapy (MTET), consisting the administration of polyphenols intravenously, either independently or in addition to conventional chemotherapies, consisting of standard and palliative chemotherapies.

Results:

Overall positive imaging response rate(in favor for metabolic response) was observed in 62%. The magnitude of response was independent of type of tumor. Among the patients who had circulating tumor cells (CTC) and/or ctDNA analyzed(number 20 and number 4 respectedly), a positive response (80% for CTC) was seen with improved CTCs and/or the ctDNA alterations for the gene variant at highest mutant allele. Reduction and normalization of plasma VEGF were seen in 92% of patients. Tolerability was good and none of the patients discontinued therapy due to toxicity.

Conclusions:

There were significant radiographic responses in advanced solid tumor cancer patients receiving MTET therapy. These changes were paralleled by the changes in serological assessment of vasculogenic factors and/or CTC/ctDNA. The high response rate is unusual for patients who have undergone multiple lines of therapy and a prospective randomized therapy of MTET is being planned.

Citation Format: M. A. Nezami, Steven Hager, Richard Lanman. Impact of multi targeted epigenetic therapy (MTET): a series of 100 consecutive advanced solid tumor cancers. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B86.