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.
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.
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.
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.