1852P - Effects of tumor treating fields (TTFields; 150 kHz) and cisplatin or pemetrexed combination therapy on mesothelioma cells in vitro and in vivo

Abstract

BackgroundMalignant pleural mesothelioma (MPM) is an aggressive thoracic cancer mostly linked to asbestos exposure. The standard of care (SOC) therapy for unresectable MPM is cisplatin plus pemetrexed. Tumor Treating Fields (TTFields) therapy is an effective anti-neoplastic treatment modality delivered via noninvasive application of low intensity, intermediate frequency, alternating electric fields. We explored the potential use of TTFields alone and in combination with cisplatin or pemetrexed as an option for MPM. MethodsCells from human mesothelioma cell lines NCI-H2052 and MSTO-211H were treated at various TTFields frequencies for 72hrs using the InovitroTM System. The combined treatment of TTFields with cisplatin or pemetrexed was tested by applying TTFields at the optimal frequency together with various drug concentrations of cisplatin or pemetrexed. Cell count, clonogenic potential, and apoptosis induction were determined. TTFields (1.2 V/cm) were applied for 8 days to rats injected intrapleurally with IL-45 cells, and overall survival (OS) was determined. ResultsThe optimal TTFields frequency was 150kHz for both human cell lines. TTFields application (1.1 V/cm, 72hrs) at 150kHz led to a 45-51% reduction in cell counts and a 46-64% additional reduction in clonogenic potential. The combined treatment of TTFields and cisplatin or pemetrexed led to a significant reduction in cell count, apoptosis induction, and clonogenic potential as compared to each modality alone (P<0.0001(. TTFields significantly prolonged the survival of rats compared to control groups. Safety studies did not reveal any adverse events associated with 150kHz TTFields application to the rat torso. ConclusionsIn these in vitro and in vivo analyses, TTFields was demonstrated to be an effective treatment for mesothelioma. TTFields in combination with cisplatin or pemetrexed further enhanced treatment efficacy. These results are consistent with the recent STELLAR phase 2 study (EF-23 trial; NCT02397928) that showed improved OS for TTFields plus SOC compared to historical control, with no increase in systemic toxicity. Legal entity responsible for the studyNovocure. FundingNovocure. DisclosureM. Munster: Full / Part-time employment: Novocure; Shareholder / Stockholder / Stock options: Novocure. K. Gotlib: Full / Part-time employment: Novocure; Shareholder / Stockholder / Stock options: Novocure. R.S. Schneiderman: Full / Part-time employment: Novocure; Full / Part-time employment: Novocure. Y. Porat: Full / Part-time employment: Novocure; Shareholder / Stockholder / Stock options: Novocure. T. Voloshin: Full / Part-time employment: Novocure; Shareholder / Stockholder / Stock options: Novocure. S. Davidi: Full / Part-time employment: Novocure; Shareholder / Stockholder / Stock options: Novocure. A. Shteingauz: Full / Part-time employment: Novocure; Shareholder / Stockholder / Stock options: Novocure. N. Kaynan: Full / Part-time employment: Novocure; Shareholder / Stockholder / Stock options: Novocure. E. Zeevi: Full / Part-time employment: Novocure; Shareholder / Stockholder / Stock options: Novocure. M. Giladi: Full / Part-time employment: Novocure; Shareholder / Stockholder / Stock options: Novocure. E.D. Kirson: Full / Part-time employment: Novocure; Shareholder / Stockholder / Stock options: Novocure. U. Weinberg: Full / Part-time employment: Novocure; Shareholder / Stockholder / Stock options: Novocure. A. Kinzel: Full / Part-time employment: Novocure; Shareholder / Stockholder / Stock options: Novocure. Y. Palti: Shareholder / Stockholder / Stock options: Novocure.