Integration of Tumor-Treating Fields into the Multidisciplinary Management of Patients with Solid Malignancies

Our plain-English summary of Integration of Tumor-Treating Fields into the Multidisciplinary Management of Patients with Solid Malignancies, by Y. Wang, M. Pandey, M.T. Ballo (The Oncologist, 2019).

The study

• Authors: Y. Wang, M. Pandey, M.T. Ballo
• Journal: The Oncologist
• Published: 2019;24(12):e1426-e1436
• Type of article: Review
• Cited by: 27 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Tumor-treating fields (TTFields) are a noninvasive antimitotic cancer treatment consisting of low-intensity alternating electric fields delivered to the tumor or tumor bed via externally applied transducer arrays. In multiple in vitro and in vivo cancer cell lines, TTFields therapy inhibits cell proliferation, disrupts cell division, interferes with cell migration and invasion, and reduces DNA repair. Human trials in patients with primary glioblastoma showed an improvement in overall survival, and trials in patients with unresectable malignant pleural mesothelioma showed favorable outcomes compared with historical control. This led to U.S. Food and Drug Administration approval in both clinical situations, paving the way for development of trials investigating TTFields in other malignancies. Although these trials are ongoing, the existing evidence suggests that TTFields have activity outside of neuro-oncology, and further study into the mechanism of action and clinical activity is required. In addition, because TTFields are a previously unrecognized antimitotic therapy with a unique mode of delivery, the oncological community must address obstacles to widespread patient and provider acceptance. TTFields will likely join surgery, systemic therapy, and radiation therapy as a component of multimodality management of patients with solid malignancies. IMPLICATIONS FOR PRACTICE: Tumor-treating fields (TTFields) exhibit a broad range of antitumor activities. Clinically, they improve overall survival for patients with newly diagnosed glioblastoma. The emergence of TTFields has changed the treatment regimen for glioblastoma. Clinicians need to understand the practical issues surrounding its use in the multidisciplinary management of patients with glioblastoma. With ongoing clinical trials, TTFields likely will become another treatment modality for solid malignancies.

© 2019 The Authors. The Oncologist published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

In plain English

This article was a review, not an original study. The authors searched PubMed for English-language articles published before February 28, 2019, along with recent conference abstracts and trial registries, on tumor-treating fields (TTFields). TTFields are low-intensity alternating electric fields delivered through arrays applied to the outside of the body. The article does not deal with asbestos exposure. For mesothelioma, the authors reported on the phase II STELLAR trial, presented at a 2018 conference. In that trial, patients given TTFields with pemetrexed and cisplatin or carboplatin had a median overall survival of 18.2 months, compared with 12.1 months in historical control, with no increase in systemic toxicity. The U.S. FDA then approved TTFields with two-drug chemotherapy for unresectable malignant pleural mesothelioma. Most of the evidence reviewed concerned glioblastoma. In the EF-14 trial of newly diagnosed patients, median overall survival was 20.5 months with TTFields plus temozolomide versus 15.6 months with temozolomide alone, and 5-year survival was 13% versus 5%. The authors noted that the highest-level clinical evidence relates to glioblastoma. They concluded that data suggest TTFields have the potential to significantly affect the lives of patients with cancer.

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: narrative review of preclinical and clinical literature on tumor-treating fields
• Who was studied: Published articles found in PubMed (English language, published before February 28, 2019), abstracts from recent cancer congresses, and ongoing trials listed on ClinicalTrials.gov and Novocure.com; the reviewed trials covered glioblastoma, malignant pleural mesothelioma, non-small cell lung cancer, ovarian cancer and pancreatic cancer
• Exposure: No asbestos exposure was studied. The treatment reviewed was TTFields: low-intensity (1 to 3 V/cm), intermediate-frequency (100 to 300 kHz) alternating electric fields delivered via externally applied transducer arrays
• Main results:
  • Reviewed STELLAR phase II trial (presented as a conference abstract): patients with mesothelioma given TTFields with pemetrexed and cisplatin or carboplatin had a median overall survival of 18.2 months, compared with 12.1 months in historical control, with no increase in systemic toxicity
  • Based on the final STELLAR data, the U.S. FDA approved TTFields (NovoTTF-100L) for use with standard two-drug chemotherapy for unresectable malignant pleural mesothelioma
  • Reviewed EF-14 phase III trial (695 patients with newly diagnosed glioblastoma; TTFields plus temozolomide n = 466, temozolomide alone n = 229): median overall survival was 20.5 vs. 15.6 months (p = .004)
  • Updated EF-14 results: 5-year overall survival was 13% with TTFields plus temozolomide vs. 5% with temozolomide alone (p = .0037)
  • Reviewed EF-11 phase III trial (237 patients with recurrent glioblastoma): median survival was 6.6 months with TTFields monotherapy vs. 6.0 months with physician's choice chemotherapy (p = .27)
  • In EF-14, mild to moderate skin irritation occurred in 43% of patients treated with TTFields, and severe (grade 3) skin reaction occurred in 2%
• The authors' conclusion: The authors concluded that, although controversies abound, data suggest TTFields have the potential to significantly affect the lives of patients with cancer
• Limitations the authors state:
  • The authors noted that the highest-level (level I) clinical evidence relates only to patients with glioblastoma

Topics

Medical terms in this study, explained in our Lexicon: Overall Survival, Unresectable, Pleural Mesothelioma, Systemic Therapy, Clinical Trial.

Related studies

• Targeted drug delivery and penetration into solid tumors — A. Corti, F. Pastorino, et al. (2012)
• 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)
• Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies — G.L. Beatty, A.R. Haas, et al. (2014)
• Mesothelin-Targeted CARs: Driving T Cells to Solid Tumors — A. Morello, M. Sadelain, et al. (2016)
• Antibody-Drug Conjugates (ADCs) for Personalized Treatment of Solid Tumors: A Review — J.M. Lambert, C.Q. Morris (2017)
• Pemetrexed disodium: a novel antifolate clinically active against multiple solid tumors — A.R. Hanauske, V. Chen, et al. (2001)

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