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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.
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(1) Purpose: Malignant pleural mesothelioma (MPM) is a rare cancer with an aggressive course. For patients who are medically inoperable or surgically unresectable, multi-agent systemic chemotherapy remains an accepted standard-of-care. The purpose of this meta-analysis is to provide baseline summative survival estimates as well as evaluate the influence of prognostic variables to provide comparative estimates for future trial designs. (2) Methods: Using PRISMA guidelines, a systematic review and meta-analysis was performed of MPM studies published from 2002-2019 obtained from the Medline database evaluating systemic therapy combinations for locally advanced or metastatic disease. Weighted random effects models were used to calculate survival estimates. The influence of proportions of known prognostic factors on overall survival (OS) were evaluated in the creation of a prognostic nomogram to estimate survival. The performance of this model was evaluated against data generated from one positive phase II study and two positive randomized trials. (3) Results: Twenty-four phase II studies and five phase III trials met the eligibility criteria; 2534 patients were treated on the included clinical studies. Ten trials included a platinum-pemetrexed-based treatment regimen, resulting in a pooled estimate of progression-free survival (PFS) of 6.7 months (95% CI: 6.2-7.2 months) and OS of 14.2 months (95% CI: 12.7-15.9 months). Fifteen experimental chemotherapy regimens have been tested in phase II or III studies, with a pooled median survival estimate of 13.5 months (95% CI: 12.6-14.6 months). Meta-regression analysis was used to estimate OS with platinum-pemetrexed using a variety of features, such as pathology (biphasic vs. epithelioid), disease extent (locally advanced vs. metastatic), ECOG performance status, age, and gender. The nomogram-predicted estimates and corresponding 95% CIs performed well when applied to recent randomized studies. (4) Conclusions: Given the rarity of MPM and the aggressive nature of the disease, innovative clinical trial designs with significantly greater randomization to experimental regimens can be performed using robust survival estimates from prior studies. This study provides baseline comparative values and also allows for accounting for differing proportions of known prognostic variables.