Abstract 1803
Background
Malignant 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.
Methods
Cells from human mesothelioma cell lines NCI-H2052 and MSTO-211H were treated at various TTFields frequencies for 72 hrs 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.
Results
The optimal TTFields frequency was 150 kHz for both human cell lines. TTFields application (1.1 V/cm, 72 hrs) at 150 kHz 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 150 kHz TTFields application to the rat torso.
Conclusions
In 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.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Novocure.
Funding
Novocure.
Disclosure
M. 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.
Resources from the same session
3371 - Pulmonary Resectable Metastases of Osteosarcoma With Apatinib and CHemotherapy (PROACH):A Multi-Center Phase II Randomized Clinical Trial
Presenter: Qiyuan Bao
Session: Poster Display session 1
Resources:
Abstract
1666 - National Clinical-biological Prospective Cohort of Incident Cases of Aggressive Fibromatosis, AF (ALTITUDES)
Presenter: Thomas Ryckewaert
Session: Poster Display session 1
Resources:
Abstract
5531 - Health-related quality Of Life In patients with advanced Soft TIssue sarcomas treated with Chemotherapy: The HOLISTIC study
Presenter: Eugenie Younger
Session: Poster Display session 1
Resources:
Abstract
5568 - Assessing QUality of life and Experiences of diagnostic Trajectories of Sarcoma patients: The QUEST study protocol
Presenter: Vicky Soomers
Session: Poster Display session 1
Resources:
Abstract