P01.028 Tumor treating fields and radiotherapy for newly diagnosed glioblastoma: Safety results from a pilot study

Tumor Treating Fields (TTFields) are a non-invasive, loco- regional, anti-mitotic treatment comprising low intensity alternating electric fields. In the phase 3 EF14 study in newly diagnosed glioblastoma (ndGBM), TTFields significantly improved survival compared to temozolomide (HR, 0.63; p<0.001). Preclinical data show that TTFields increase glioma cells undergoing cellular death following radiotherapy (RT) by inhibiting DNA damage repair. This suggests TTFields have a radiosensitizing effect and can increase the efficacy of RT. The current study was the first to test TTFields administered concomitant to RT in ndGBM patients. Ten patients with ndGBM were enrolled in this single-arm trial. All had recovered from maximal debulking surgery or biopsy and had KPS ≥70. Patients started TTFields prior to or at the time of RT, and were on stable or decreasing doses of corticosteroids for 7 days before enrollment. TTFields (200kHz) were delivered for 18 hours/day with daily removal of the transducer arrays during delivery of RT. Temozolomide was administered at 75 mg/m2/daily for 6 weeks and RT at a total dose of 60 Gy. The primary endpoint was safety of the combined therapies. Ten patients were enrolled at a single center between April and December 2017. Median age was 59 (range 42–71 years), median KPS was 90 (range 80–100) and 8 (80%) of patients were male. Five patients (50%) underwent gross total resection while the rest had biopsy only. Median dose of RT was 60 Gy (range 52–60 Gy). Six patients (60%) have reported have an adverse event (AE) to-date. The most common AE was TTFields-related skin toxicity, reported in 4 (40%) of the patients. None of these were severe. All other AEs reported occurred in one patient only and could be attributed to the underlying disease or chemotherapy. Two reported serious AEs (seizures and general deterioration) were considered unrelated to TTFields. The proportion of patients with TTFields-related skin toxicity (40%) was similar to that reported for the 466 TTFields patients treated with TTFields in the phase III study (52%), where patients started TTFields > 4 weeks after RT. No other TTFields-related toxicities were reported, nor was there an increase in RT- or temozolomide-related toxicities as a result of combining TTFields with these therapies. To date, TTFields has demonstrated a high safety profile when combined with other therapies in newly diagnosed GBM.