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
3157 - Efficacy and safety of anlotinib in advanced leiomyosarcoma: Subgroup analysis of a phase IIB trial (ALTER0203)
Presenter: Yihebali Chi
Session: Poster Display session 1
Resources:
Abstract
3710 - The effect of treatment line on the efficacy of Anlotinib hydrochloride in advanced alveolar soft part sarcoma patients
Presenter: Zhiwei Fang
Session: Poster Display session 1
Resources:
Abstract
3184 - Prior exposure to pazopanib (PAZ) did not minor efficacy of regorafenib (REG) in non-adipocytic soft tissue sarcoma patients (pts)
Presenter: Nicolas Penel
Session: Poster Display session 1
Resources:
Abstract
798 - Pexidartinib (Pex) for locally advanced tenosynovial giant cell tumor (TGCT): characterization of hepatic adverse reactions (ARs)
Presenter: Sebastian Bauer
Session: Poster Display session 1
Resources:
Abstract
6117 - VEGFR2 and ITGA polymorphisms as novel pan-sarcoma biomarkers for sensitivity prediction as well as toxicity prevention anti-angiogenesis therapy in pediatric and young adult
Presenter: Qiyuan Bao
Session: Poster Display session 1
Resources:
Abstract
5450 - Reversion of resistance to mTOR inhibitors with the addition of exemestane in patients with malignant PEComa.
Presenter: Roberta Sanfilippo
Session: Poster Display session 1
Resources:
Abstract
4279 - Efficacy and Safety of VEGFR2 Inhibitor Apatinib combined with chemotherapy for Sarcoma in Stage IV
Presenter: Zhiwu Ren
Session: Poster Display session 1
Resources:
Abstract
5929 - Outcomes of metastatic soft tissue sarcoma treated with Pazopanib from dedicated medical oncology sarcoma clinic: A holistic care approach from a developing country
Presenter: Akhil Kapoor
Session: Poster Display session 1
Resources:
Abstract
2469 - Inhibition of mTOR signaling enhances Trabectedin activity in Soft Tissue Sarcoma
Presenter: David Moura
Session: Poster Display session 1
Resources:
Abstract
4210 - Efficacy and safety of apatinib for advanced gastrointestinal stromal tumors after failure of imatinib and sunitinib: An open-label, multicenter, single-arm, phase II trial
Presenter: Zhaolun Cai
Session: Poster Display session 1
Resources:
Abstract