198P - Efficacy of 150 kHz tumor treating fields (TTFields) and cisplatin or pemetrexed for the treatment of mesothelioma cells in vitro

Abstract

Background: Malignant pleural mesothelioma (MPM) is a rare and aggressive thoracic cancer that has been strongly linked to asbestos exposure. The standard of care treatment for unresectable mesothelioma is cisplatin plus pemetrexed chemotherapy, which offers modest outcomes. Thus, there is an urgent need to identify more effective treatments for mesothelioma patients. 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 a treatment for mesothelioma. Methods: NCI-H2052 and MSTO-211H cells were treated at various TTFields frequencies for 72 hours using the inovitro system. Results: The optimal TTFields frequency leading to the highest reduction in cell counts was 150 kHz for both NCI-H2052 and MSTO-211H cells. TTFields application (1.1 V/cm, 72 hours) at 150 kHz led to 45%, 51% reduction in cell counts and 64%, 46% reduction in clonogenic potential in NCI-H2052 and MSTO-211H cells, respectively. Efficacy of the combined treatment of TTFields and cisplatin or pemetrexed was tested by applying TTFields at the optimal frequency together with various drug concentrations. The combined treatment of TTFields and cisplatin or pemetrexed led to a significant reduction in cell count, induction of apoptosis and reduced clonogenic potential as compared to either modality alone (2-way ANOVA, p < 0.0001(. Safety studies did not reveal any adverse event associated with 150 kHz TTFields application to the rat torso. Conclusions: These results demonstrate that TTFields can be an effective treatment against mesothelioma cells and that the combination with cisplatin or pemetrexed may further enhance treatment efficacy. These results are supported by a recent phase 2 study, which reported that MPM patients treated with the combination of TTFields with pemetrexed and platinum experienced improved overall survival as compared to historical control with no increase in systemic toxicity. Legal entity responsible for the study: Novocure Israel. Funding: Novocure Israel. Disclosure: U. Weinberg, M. Munster, R.S. Schneiderman, Y. Porat, T. Voloshin Sela, A. Shteingauz, E. Zeevi, M. Giladi, A. Kinzel, Y. Palti: Full time employee, stock options, stock ownership: Novocure Israel. K. Gotlib, S. Davidi, N. Kaynan: Full time employee, stock options: Novocure Israel. E. Kirson: Full time employee stock options, stock ownership: Novocure Israel; Holds senior leadership position: Novocure Israel.