Feasibility of Tumor Treating Fields with Pemetrexed and Platinum-Based Chemotherapy for Unresectable Malignant Pleural Mesothelioma: Single-Center, Real-World Data

Abstract

Purpose: The objectives of this study were to evaluate the implementation, device usage rates, clinical outcomes, and treatment-related toxicities associated with TTFields and pemetrexed plus platinum-based chemotherapy in patients with unresectable MPM, outside the initial trial results. Methods: Consecutive patients with unresectable MPM were enrolled onto an FDA-required HDE protocol from 2019 to 2021. All patients were treated with a protocol-defined regimen of continuous TTFields (150 kHz) and pemetrexed plus platinum-based chemotherapy. Results: Five patients with unresectable MPM were enrolled. The median number of 4-week TTFields cycles was 5 (range: 2–7 cycles). Median TTFields device usage in the first 3 months was 12.5 h per day (range: 5–16.8 h), representing 52% (21–70%) of the potential daily duration. The median follow-up was 5.4 months (range: 1.1–20.9 months). Treatment-related dermatitis was the only side effect associated with TTFields and was reported as grade 1–2 in all patients; no patient had grade 3+ device-related toxicities. Conclusions: This study represents the first results of real-world implementation of TTFields for MPM. In comparison to the initial clinical trial (STELLAR), compliance rates were lower, although skin-related toxicities appeared similar. Further initiatives and guidelines should be developed to manage treatment-related dermatitis and improve device usage.

Expert guidance on prophylaxis and treatment of dermatologic adverse events with Tumor Treating Fields (TTFields) therapy in the thoracic region

“…The most common types are contact dermatitis, pruritus, hyperhidrosis, pressure necrosis, and skin erosions (Figure 2; Supplementary Figure S1). Findings from clinical studies have demonstrated that most skin AEs are mild and manageable without the need to significantly disrupt treatment (3,4,10), which is supported by real-world data (17,26). Although analysis of skin AEs from pilot studies has not identified any correlation between select risk factors and the occurrence of TTFields therapy-related skin AEs (Table 1), several factors may increase the risk and severity of skin damage.…”

“…The most common adverse events (AEs) associated with TTFields therapy are dermatologic AEs, as reported in both clinical studies and recent real-world data ( 7 , 9 – 12 , 14 , 17 ). Advice on the prevention and management of dermatologic scalp AEs associated with TTFields therapy are available; however, no such guidance exists for the thoracic region, which is especially needed as skin AEs in the thoracic region are often exacerbated from the motion of respiration ( 18 ).…”

Novel Insights Into Mesothelioma Therapy: Emerging Avenues and Future Prospects

“…TT Fields at a frequency of 150 kHz exhibited the highest cytotoxicity to mesothelioma cells, led to an enhanced number of DNA double-strand breaks, and diminished expression of Fanconi Anemia (FA)-BRCA DNA repair pathway proteins. The co-treatment of TT Fields with cisplatin or pemetrexed significantly enhanced treatment efficacy (56,57). Nevertheless, there are a few limitations of the STELLAR study that should be mentioned.…”

The Nephrotoxicity of Drugs Used in Causal Oncological Therapies

“…This process takes place both in normal (healthy) and cancer cells [ 53 ]. This drug has found application in the treatment of lung (NSCLC) and pleura (mesothelioma) cancers [ 53 , 54 ]. The nephrotoxic effect has its pathomechanism in inducing stromal fibrosis, interstitial edema, and vacuolization of proximal tubular cells with the retained glomerular structure [ 13 , 55 , 56 ].…”