Tumor Treating Fields (TTFields) are a non-invasive, loco-regional, antimitotic treatment modality, which have been approved for the treatment of glioblastoma (GBM) by the FDA. TTFields are delivered to the tumor via transducer arrays applied to the skin surrounding the tumor. The only TTFields-related adverse event (AE) reported in Phase III GBM trials was localized dermatitis beneath the arrays. The safety of TTFields has also been investigated in non-small-cell lung cancer (NSCLC), mesothelioma, pancreatic and ovarian cancer. No TTFields-related serious AEs were reported in these studies. Here we present a meta-analysis of AEs reported across clinical studies conducted to date, where TTFields were applied to the torso.
Methods: 192 patients from 4 pilot studies were included in the analysis: EF-15 (n=41, advanced NSCLC), PANOVA-2 (n=40, advanced pancreatic adenocarcinoma), STELLAR (n=80, malignant pleural mesothelioma) and INNOVATE (n=31, recurrent ovarian carcinoma). The frequency of TTFields applied was 150 kHz in all except 200kHz in the INNOVATE study. The compliance required per protocol with TTFields was 12 hours/day on average in EF-15, and 18 hours/day in the other trials. All patients received standard of care systemic chemotherapy for their disease in addition to TTFields. AEs, their severity and frequency, and their association with the experimental treatment were reported using CTCAE Version 4, except for EF-15, where CTCAE version 3 was used. Toxicities were reported as incidence by body system and MedDRA term in the number of patients who received any amount of TTFields treatment.
Results: The median age was 63 (range: 44-78), 73 (49-81), 67 (27-78) and 60 (45-77) for EF-15, PANOVA-2, STELLAR and INNOVATE, respectively. Patients enrolled in the trials had an ECOG score of 0-1, except for 7 patients enrolled in the EF-15 study with ECOG score of 2. Low grade gastrointestinal (GI) toxicities reported with an incidence ≥5%: constipation (16%), diarrhea (14%), nausea (27%), vomiting (13%). None of the GI toxicities was associated with TTFields, and the incidence of high-grade GI toxicities did not reach 10%. Low grade disorders such as asthenia (12%), fatigue (18%) and anorexia (2%) were common (<20%) but not associated with TTFields. Both low and high grade dyspnea (11% and 5%, respectively) were reported. The incidence of different types of arrhythmia was <2%. 58% of the patients had dermatological AE. Low grade dermatitis was reported in 53% of the patients, while high grade in only 6%. 9% of patients reported low grade pruritus.
Conclusions: No new safety signals were identified following the meta-analysis of adverse events from pilot clinical studies, in which TTFields were applied to the torso. The incidence of TTFields-related skin toxicity was similar to that reported in glioblastoma patients. The application of TTFields to the torso is safe.
Citation Format: Giovanni Luca Ceresoli, Ignace Vergote, Fernando Rivera, Miklos Pless. Safety of Tumor Treating Fields delivery to the torso: Pooled analysis from TTFields clinical trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT202.