Abstract CT105: The safety of TTFields applied to the torso: A meta-analysis of 176 patients from four phase I-II trials
Authors: Vergote Ignace , Benavides Manuel , Pless Miklos , Ceresoli Giovanni 
Published: August 2018

Abstract
Tumor Treating Fields (TTFields) is a non-invasive, loco-regional, antimitotic treatment modality, approved for treatment of glioblastoma. TTFields are delivered to the tumor through transducer arrays applied non-invasively to the region of the body with the highest tumor burden. In a phase 3 trial in newly diagnosed glioblastoma (GBM), addition of TTFields to temozolomide was not associated with any significant increase in rates of systemic adverse events (AEs) versus temozolomide alone. The only common treatment related AE seen in TTFields-treated patients was localized dermatitis underneath the arrays. Mild-moderate dermatitis was reported in 52% of patients (2% had grade 3 skin toxicity). The safety of TTFields was investigated in four phase I-II studies for malignancies located outside of the brain: non-small-cell lung cancer (NSCLC), mesothelioma, pancreatic cancer and ovarian cancer.
Methods
Four phase I-II clinical studies of TTFields were included in the analysis: EF-15 (n=41, advanced NSCLC; combined with pemetrexed), PANOVA (n=40, advanced pancreatic adenocarcinoma; combined with gemcitabine with or without nab-paclitaxel), STELLAR (n=64, malignant pleural mesothelioma; combined with platinum and pemetrexed) and INNOVATE (n=31, recurrent ovarian carcinoma; combined with weekly paclitaxel). The frequency of TTFields applied was 150-200 kHz depending on tumor histology. The compliance required per protocol with TTFields was 12 - 18 hours/day. All patients received standard of care systemic chemotherapy for their disease in addition to TTFields. Severity and frequency of AEs, and association with the experimental treatment were evaluated using CTCAE criteria.
Results
The median age of patients was 69 (range: 41-81), 73 (49-81), 68 (43-78) and 60 (45-77) for EF-15, PANOVA, 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. The incidence of grade 1-2 gastrointestinal (GI) toxicities was ≥5%: constipation (16%), diarrhea (14%), nausea (27%) and vomiting (13%). GI toxicity was related to standard chemotherapy or underlying disease in all cases. Grade 1-2 general disorders such as asthenia, fatigue and anorexia were common but less than 20% for each, and were related to the underlying disease or standard chemotherapy. Grade 3-4 dyspnea (6%) was reported in patients with lung tumors, related to exacerbation of the underlying disease. The incidence of all types of arrhythmias was ≤2% and none were severe. The only common TTFields related adverse event was dermatitis beneath the device transducer arrays. Half of the patients (50%) had grade 1-2 dermatitis, while grade 3 dermatitis was seen in 6% of patients. 7% of patients complained of grade 1-2 pruritus. Dermatologic AEs were managed using published guidelines leading to full resolution in all cases.
Conclusions
Treatment of solid tumor patients with TTFields at 150-200 kHz to the lungs, abdomen and upper pelvis did not result in treatment related pulmonary, cardiac, hematological or gastrointestinal toxicity. Expected dermatological toxicity beneath the device transducer arrays was seen in half of the patients, and resolved after treatment termination in all cases.
Citation Format: Ignace Vergote, Manuel Benavides, Miklos Pless, Giovanni Ceresoli. The safety of TTFields applied to the torso: A meta-analysis of 176 patients from four phase I-II trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT105.