Tumor Treating Fields: Will the Evidence Gap Ever Be Filled?

Tumor Treating Fields (TTFs) deliver low-intensity electric fields through adhesive skin arrays and have been approved in different oncology indications. However, concerns remain regarding the evidence supporting their benefit. Here, we highlight four limitations. First, TTFields utilization includes 24/7 assistance, home deliveries, and regular home-based interactions for array changes. In the absence of sham-controlled randomized trials, the device equivalent of placebo-controlled trials, the specific contribution of TTFields cannot be distinguished from the additional supportive care and infrastructure accompanying device use. Second, although a mechanistic rationale exists, the biological plausibility remains limited, particularly because of the lack of validated human in vivo dosimetry data. Third, while reviewing the six pivotal trials that supported approvals, we describe the use of suboptimal control arms in half of them, which limits their external validity. Fourth, we describe occurrences of protocol changes and intriguing censoring patterns, both raising questions about study conduct. The specificities of regulatory pathways for medical devices permit greater evidentiary flexibility than for drugs, while post-market evidence generation remains insufficiently transparent. In contrast to most other types of devices, a single company, Novocure, controls the main evidence base for with little to no independent or competing involvement. High-quality sham-controlled trials and harmonized post-market obligations are needed to isolate the specific contribution of TTFs and establish whether they provide genuine therapeutic benefit.