Tumor Treating Fields (TTFields) Therapy in Unresectable Pleural Mesothelioma: Overview of Efficacy, Safety, and Future Outlook

Our plain-English summary of Tumor Treating Fields (TTFields) Therapy in Unresectable Pleural Mesothelioma: Overview of Efficacy, Safety, and Future Outlook, by G.L. Ceresoli, L. Gianoncelli (Current Treatment Options in Oncology, 2025).

The study

• Authors: G.L. Ceresoli, L. Gianoncelli
• Journal: Current Treatment Options in Oncology
• Published: 2025;26(5):398-414
• Type of article: Review
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Pleural mesothelioma is an incurable cancer with unmet diagnostic and therapeutic needs. Due to its pattern of local spread, few patients are candidates for multimodality treatment and thus most patients only receive systemic therapy. Chemotherapy (pemetrexed plus platinum) was standard of care until the recent addition of immunotherapy (nivolumab plus ipilimumab, or pembrolizumab plus chemotherapy) as further first-line option. Physicians treating pleural mesothelioma should be aware of another option with Tumor Treating Fields (TTFields) therapy, a locoregionally-applied therapy utilizing electric fields generated by a portable medical device, and delivered to the tumor by skin-placed arrays. TTFields therapy delivered to the thorax using the NovoTTF- 100L device concomitant with pemetrexed and platinum agent is approved for unresectable pleural mesothelioma in the US, and received Conformité Européenne certification in Europe, based on results from the phase 2 STELLAR study (EF- 23; NCT02397928), where TTFields-related toxicity was limited to mild-to-moderate reversible skin reactions. Overall survival in the STELLAR study with TTFields therapy was 18.2 months, with further post-hoc analysis showing extended survival in patients with epithelioid histology. Within the evolving landscape of systemic treatments, TTFields therapy represents a novel and clinically versatile therapeutic option in the battle against pleural mesothelioma without introducing additional toxicities other than mild-to-moderate skin irritation. While promising, additional research is needed to optimize clinical application of TTFields therapy in patients with pleural mesothelioma, such as identifying the molecular determinants of therapy efficacy, and further investigation into the safe and effective delivery of TTFields therapy together with systemic agents, including immunotherapies.

© 2025. The Author(s).

In plain English

This article was a review, not a new study. It described Tumor Treating Fields (TTFields) therapy, which uses a portable device to deliver electric fields through patches (arrays) placed on the skin around the tumor, for people with unresectable pleural mesothelioma. The authors described pleural mesothelioma as an asbestos-related tumor. The review covered laboratory and animal research and earlier clinical studies. Its main clinical evidence was the earlier STELLAR trial, a single-arm phase 2 study in which 80 patients at 12 European sites received TTFields with pemetrexed and platinum chemotherapy. In STELLAR, median overall survival was 18.2 months. It was 21.2 months for patients with epithelioid tumors and 12.1 months for those with non-epithelioid tumors. The only device-related side effect was skin irritation under the arrays. Four patients (5%) had a grade 3 skin reaction. The authors noted that STELLAR had the limitations of a single-arm phase 2 study, including possible sampling bias. They concluded that TTFields offers an additional treatment option without added toxicity beyond mild-to-moderate skin irritation, and that more research is needed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review (narrative review of mechanism, preclinical evidence, and clinical use of TTFields in pleural mesothelioma); no new data were generated
• Who was studied: Published research reviewed. The main clinical study reviewed was STELLAR: 80 patients with untreated, unresectable pleural mesothelioma, enrolled at 12 European sites from February 2015 to March 2017
• Exposure: The exposure studied was a treatment, not asbestos. It was TTFields therapy (electric fields delivered by a portable device through skin-placed arrays) applied to the thorax at 150 kHz for a planned at least 18 hours per day, given with pemetrexed and platinum (cisplatin or carboplatin) chemotherapy. Asbestos was mentioned only in describing pleural mesothelioma as an asbestos-related tumor; no fiber types or asbestos exposures were studied.
• Main results:
  • STELLAR trial (80 patients), as reported in this review: median overall survival was 18.2 months, 62% were alive at 1 year, and 2-year overall survival was 42%
  • STELLAR trial: median overall survival was 21.2 months in patients with epithelioid tumors versus 12.1 months in patients with non-epithelioid tumors
  • STELLAR trial: median progression-free survival was 7.6 months in the overall study population
  • STELLAR trial, among 72 patients with an evaluable response: partial responses in 29 patients (40%); partial response or stable disease in 70 patients (97%)
  • STELLAR trial: grade 1 to 2 skin reactions occurred in 53 patients (66%), and four patients (5%) had a grade 3 skin adverse event
  • STELLAR trial: over the first 3 months, median device use was 16.3 hours per day, slightly below the recommended 18 hours
  • A meta-analysis of 192 patients from four pilot studies of TTFields to the torso (including STELLAR) reported device-related skin adverse events in 58% of patients
• The authors' conclusion: The authors concluded that TTFields therapy gives an additional treatment option for pleural mesothelioma without additional toxicities other than mild-to-moderate skin irritation. They also concluded that further research is needed, including on combining TTFields with other systemic therapies and on the molecular determinants of efficacy.
• Limitations the authors state:
  • STELLAR was a single-arm phase 2 study with possible sampling bias in a heterogeneous cancer
  • Few data exist on how the duration of daily device use relates to outcomes in pleural mesothelioma
  • Apart from histology, it is not known whether any biomarkers or mutations predict response

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Tumor Treating Fields (TTFields), Unresectable Pleural Mesothelioma, Pleural Mesothelioma, Systemic Therapy, Chemotherapy, Pemetrexed (Alimta), Immunotherapy, Nivolumab (Opdivo).

Related studies

• Efficacy and immunogenic effects of Tumor Treating Fields (TTFields) in preclinical models of pancreatic ductal adenocarcinoma, with and without gemcitabine/nab-paclitaxel — T. Kan, T. Haj Khalil, et al. (2026)
• Tumour treating fields therapy for glioblastoma: current advances and future directions — O. Rominiyi, A. Vanderlinden, et al. (2021)
• The safety profile of Tumor Treating Fields (TTFields) therapy in glioblastoma patients with ventriculoperitoneal shunts — N.A. Oberheim-Bush, W. Shi, et al. (2022)
• The Mechanisms of Action of Tumor Treating Fields — J.C. Moser, E. Salvador, et al. (2022)
• Tumor Treating Fields (TTFields) downregulate the Fanconi Anemia-BRCA pathway and increase the efficacy of chemotherapy in malignant pleural mesothelioma preclinical models — H. Mumblat, A. Martinez-Conde, et al. (2021)
• Expert guidance on prophylaxis and treatment of dermatologic adverse events with Tumor Treating Fields (TTFields) therapy in the thoracic region — M.J. Anadkat, M. Lacouture, et al. (2022)

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