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
1269 - One-year follow-up results of eribulin for soft-tissue sarcoma including rare subtypes in a real-world observational study in Japan
Presenter: Shunji Takahashi
Session: Poster Display session 1
Resources:
Abstract
2868 - Prevalence of chemotherapy use and its impact on overall survival in patients with bone- and soft tissue sarcomas -A population-based analysis of 3746 patients
Presenter: Herbert Loong
Session: Poster Display session 1
Resources:
Abstract
3042 - Clinical course and therapeutic management of classical and endemic Kaposi’s Sarcoma (C/E KS)
Presenter: Lina Benajiba
Session: Poster Display session 1
Resources:
Abstract
3141 - The final outcomes of study on combined therapy of adult patients with localized synovial sarcoma
Presenter: Katarzyna Kozak
Session: Poster Display session 1
Resources:
Abstract
5449 - Real-world Outcomes of Patients with Locally Advanced or Metastatic Epithelioid Sarcoma
Presenter: Mrinal Gounder
Session: Poster Display session 1
Resources:
Abstract
4465 - SAKK 57/16 Nab-Paclitaxel And Gemcitabine in soft tissue sarcoma (NAPAGE): results from the phase I part of a phase I/II trial
Presenter: Antonia Digklia
Session: Poster Display session 1
Resources:
Abstract
5013 - Outcome of 98 patients with epithelioid sarcoma treated in curative intent: a retrospective study from the French Sarcoma Group (GSF-GETO)
Presenter: Maud Pedrono
Session: Poster Display session 1
Resources:
Abstract
5614 - Comparison of filgrastim and pegfilgrastim prophylaxis in sarcoma patients receiving highly myelosuppressive chemotherapy.
Presenter: Paolo Tarantino
Session: Poster Display session 1
Resources:
Abstract
1033 - Access to clinical trials for soft tissue sarcoma patients in Western and Eastern Europe
Presenter: Vasilii Ostafiichuk
Session: Poster Display session 1
Resources:
Abstract
4094 - Treatment outcomes for adult patients with localized osteosarcoma treated with chemotherapy without methotrexate
Presenter: Marília Silva
Session: Poster Display session 1
Resources:
Abstract