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
3683 - Impact of Radiotherapy on efficacy of anti-programmed death 1 (PD-1) antibodies in metastatic NSCLC
Presenter: Evangeline Samuel
Session: Poster Display session 1
Resources:
Abstract
3924 - Pembrolizumab frontline monotherapy in patients with NSCLC and high PD-L1 expression: Real World Data from a European Cohort with focus on subgroups of interest
Presenter: Giannis Mountzios
Session: Poster Display session 1
Resources:
Abstract
3970 - Patients with metastatic non-small cell lung cancer and PD-L1 expression in Germany. Treatment and first outcome from the prospective German Registry Platform CRISP (AIO-TRK-0315)
Presenter: Martin Sebastian
Session: Poster Display session 1
Resources:
Abstract
5350 - The efficacy and safety of pembrolizumab as a first-line therapy in PD-L1 50% positive advanced NSCLC (HOPE-001)
Presenter: Motohiro Tamiya
Session: Poster Display session 1
Resources:
Abstract
3832 - Osimertinib in epidermal growth factor receptor (EGFR) T790M advanced non-small cell lung cancer (NSCLC): analysis of patients with central nervous system (CNS) metastases in a real-world study (ASTRIS)
Presenter: Giulio Metro
Session: Poster Display session 1
Resources:
Abstract
4082 - Real-world (RW) treatment patterns and outcomes for second-line (2L) therapy and beyond in patients (pts) with epidermal growth factor receptor-mutated (EGFRm) advanced NSCLC receiving a first-line (1L) first- or second-generation (1G/2G) EGFR tyrosine kinase inhibitor (TKI)
Presenter: Riyaz Shah
Session: Poster Display session 1
Resources:
Abstract
2855 - Impact of ramucirumab (RAM) + erlotinib (ERL) on EGFR mutations in circulating tumor DNA – The 1st report of a biomarker study in Japanese patients from RELAY: Global Ph3 study of ERL + RAM or placebo (PL) in 1L metastatic NSCLC with EGFR activating mutations
Presenter: Kazuto Nishio
Session: Poster Display session 1
Resources:
Abstract
2911 - Apatinib combined with EGFR - TKI in treating advanced non-small cell lung cancer with EGFR - TKI resistance
Presenter: Ruifen Tian
Session: Poster Display session 1
Resources:
Abstract
2100 - Updated analysis of a phase I trial of afatinib (Afa) and bevacizumab (Bev) in chemo-naïve patients (pts) with advanced non-small-cell lung cancer (NSCLC) harboring EGFR-mutations: OLCSG1404
Presenter: Takashi Ninomiya
Session: Poster Display session 1
Resources:
Abstract
4325 - Multiple synchronous mechanisms may contribute to osimertinib resistance in non-small cell lung cancer (NSCLC) patients: insights of the MATCH-R study
Presenter: Diego Enrico
Session: Poster Display session 1
Resources:
Abstract