Tumour Treating Fields in combination with pemetrexed and cisplatin or carboplatin as first-line treatment for unresectable malignant pleural mesothelioma (STELLAR): a multicentre, single-arm phase 2 trial

Ceresoli, Giovanni Luca; Aerts, Joachim; Dziadziuszko, Rafał; Ramlau, Rodryg; Cedrés, S.; Meerbeeck, Jan P. van; Mencoboni, Manlio; Planchard, David; Chella, Antonio; Crinò, Lucio; Krzakowski, Maciej; Rüssel, Jörn; Maconi, Antonio; Gianoncelli, Letizia; Grosso, Federica

doi:10.1016/s1470-2045(19)30532-7

Cited by 111 publications

(103 citation statements)

References 28 publications

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“…Clinical trials with TTFields in other solid malignancies are ongoing. TTFields (150 kHz) in combination with chemotherapy was recently approved by the FDA for first-line treatment of unresectable malignant pleural mesothelioma based on results from the STELLAR trial (55). Dermatologic AEs were also the main TTFields-related AE reported in that trial (68% in total, with 66% as grade 1/2).…”

Section: Discussionmentioning

confidence: 99%

Prevention and Management of Dermatologic Adverse Events Associated With Tumor Treating Fields in Patients With Glioblastoma

et al. 2020

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Importance: Tumor Treating Fields (TTFields) are an anti-mitotic treatment approved for treating newly diagnosed and recurrent glioblastoma, and mesothelioma. TTFields in glioblastoma comprise alternating electric fields (200 kHz) delivered continuously, ideally for ≥18 h/day, to the tumor bed via transducer arrays placed on the shaved scalp. When applied locoregionally to the tumor bed and combined with systemic temozolomide chemotherapy, TTFields improved overall survival vs. temozolomide alone in patients with newly diagnosed glioblastoma. Improved efficacy outcomes with TTFields were demonstrated, while maintaining a well-tolerated and manageable safety profile. The most commonly-reported TTFields-associated adverse events (AEs) are beneath-array dermatologic events. Since survival benefit from TTFields increases with duration-of-use, prevention and management of skin AEs are critical to maximize adherence. This paper describes TTFields-associated dermatological AEs and recommends prevention and management strategies based on clinical trial evidence and real-world clinical experience. Observations: TTFields-associated skin reactions include contact dermatitis (irritant/allergic), hyperhidrosis, xerosis or pruritus, and more rarely, skin erosions/ulcers and infections. Skin AEs may be prevented through skin-care and shifting (∼2 cm) of array position during changes. TTFields-related skin AE management should be based on clinical phenotype and severity. Depending on diagnosis, recommended treatments include antibiotics, skin barrier films, moisturizers, topical corticosteroids, and antiperspirants. Water-based lotions, soaps, foams, and solutions with minimal impact on electrical impedance are preferred with TTFields use over petroleum-based ointments, which increase impedance. Conclusions: Early identification, prophylactic measures, and symptomatic skin AE management help patients maximize TTFields usage, while maintaining quality-of-life and optimizing therapeutic benefit. Lacouture et al. Managing TTFields-Associated Skin Adverse Events Implications for practice: TTFields confer a survival benefit in patients with glioblastoma that correlates positively with duration of daily use. Skin events (rash) are the primary treatment-related AE that can limit duration of use. The recommendations described here will help healthcare professionals to recognize, prevent, and manage dermatologic AEs associated with TTFields treatment. These recommendations may improve cutaneous health and support adherence to therapy, both of which would maximize treatment outcomes.

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Section: Discussionmentioning

confidence: 99%

Prevention and Management of Dermatologic Adverse Events Associated With Tumor Treating Fields in Patients With Glioblastoma

et al. 2020

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“…Given that the targets of TTFields are generic and primarily tumor-type nonspecific, TTFields may offer advantages in various other cancers including GBM. To study that clinical probability research is ongoing to investigate TTFields in many other solid tumors, including colorectal, pancreatic, ovarian, non-small cell lung carcinoma (NSCLC), brain metastases from NSCLC, and malignant mesothelioma for future cancer therapy [24][25][26][27][28]. A recent TTFields study shows that it may also block DNA damage repair, cellular migration, and invasion [29], and regulate autophagy [30].…”

Section: Discussionmentioning

confidence: 99%

5-Fluorouracil as a Tumor-Treating Field-Sensitizer in Colon Cancer Therapy

Lee

Cho

Sai³

et al. 2019

Cancers

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Colorectal cancer (CRC) is a major cause of mortality that can be treated effectively with chemotherapy and radiotherapy, although resistance to these therapeutic modalities often occurs. Tumor-treating fields (TTFields) can block tumor growth by selectively impairing tumor cell division. In this study, we investigated the mechanism by which 5-fluorouracil (5-FU) sensitizes tumor cells to TTFields. Human HCT116 and SW480 CRC cells were treated with 5-FU and/or TTFields, and characterized in vitro in terms of cell viability, apoptosis through reactive oxygen species production, autophagy, and metastatic potentials. The biological effects of 5-FU and/or TTFields were studied via positron emission tomography and computed tomography on xenograft tumor growth and were confirmed with organoid models of patients. Our results revealed that combination treatment with 5-FU and TTFields increased the efficiency of TTFields therapy in colon cancer cells by downregulating signaling pathways associated with cell proliferation, survival, cell invasion, and migration while upregulating pathways mediating apoptosis and autophagic cell death. The novel mechanistic insights gleaned in this study suggest that combination therapy with TTFields and 5-FU may be effective in treating CRC, although safety and efficacy testing in patients with CRC will need to be performed before this strategy can be implemented clinically for TTF-sensitization.

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“…Critiques can be grouped mainly as (1) inadequacy of trial design lacking a “sham” device, with the finding of statistical significance potentially representing a false-positive result; (2) a mechanism of action that remains incompletely elucidated despite repeated explanation; (3) lack of a biomarker predicting the subpopulation most likely to benefit; (4) high cost to the health care system estimated as between $150 000 and $615 000 per life-year gained, 13 , 14 regardless of the payer; (5) a “hassle” factor associated with its usage, 15 notwithstanding secondary analyses demonstrating no obvious reduction in overall health-related quality of life 16 ; and (6) inescapable breach of privacy regarding the diagnosis of a brain tumor during device usage in public, an issue partially addressed through the covering of the device by clothing when treating cancers arising outside the brain, such as mesothelioma. 17 Cumulatively, these factors result in the overarching concern that the perceived benefit may be low relative to other therapies and patient inconvenience ( Table 1 ) and reinforce our concern that the EF-14 trial participants were highly selected and motivated patients who consented to participate, 10 and may accordingly not represent the broader population of patients with GBM. Uptake in the field remains far from universal.…”

mentioning

confidence: 83%

Current usage of tumor treating fields for glioblastoma

Lassman

Joanta-Gomez²,

Pan

et al. 2020

Neuro-Oncology Advances

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Abstract Background Tumor Treating Fields (TTF) have entered clinical practice for newly diagnosed and recurrent glioblastoma (GGM). However, controversies remain unresolved with regard to appropriate usage. We sought to determine TTF usage in major academic neuro-oncology programs in New York City, USA and Heidelberg, Germany and understand current attitudes toward TTF usage among providers. Methods We retrospectively determined TTF usage among patients with GGM, before and since the publication of key clinical trial results and regulatory approvals. We also surveyed attendees of an educational session related to TTF during the 2019 American Society of Clinical Oncology annual meeting. Results TTF usage remains infrequent (3–12% of patients with newly diagnosed GBM, and 0–16% of patients with recurrent disease) in our practices, although it has increased over time. Among 30 survey respondents (77% of whom self-identified as neuro- or medical oncologists), 60% were convinced that TTF prolongs survival for newly diagnosed GGM despite published phase III data and regulatory approval, and only 30% viewed TTF as definitively part of the standard of care treatment. A majority (87%) opposed mandating TTF incorporation into the design of clinical trials. Conclusions Providers continue to view TTF with some level of skepticism, with a lack of additional supportive data and logistical concerns representing continued barriers to uptake.

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Tumour Treating Fields in combination with pemetrexed and cisplatin or carboplatin as first-line treatment for unresectable malignant pleural mesothelioma (STELLAR): a multicentre, single-arm phase 2 trial

Cited by 111 publications

References 28 publications

Prevention and Management of Dermatologic Adverse Events Associated With Tumor Treating Fields in Patients With Glioblastoma

Prevention and Management of Dermatologic Adverse Events Associated With Tumor Treating Fields in Patients With Glioblastoma

5-Fluorouracil as a Tumor-Treating Field-Sensitizer in Colon Cancer Therapy

Current usage of tumor treating fields for glioblastoma

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