Abstract CT086: Safety of TTFields and radiotherapy (RT) for newly diagnosed glioblastoma: Interim safety results from a pilot study
Authors: Grossman Rachel , Ram Zvi 
Published: August 2018

Abstract
Background: Tumor Treating Fields (TTFields) are a non-invasive, loco- regional, anti-mitotic treatment modality, based on delivery of low intensity alternating electric fields to the tumor. Efficacy of TTFields in newly diagnosed glioblastoma patients has been demonstrated in a phase 3 clinical study (Stupp R., et al., JAMA 2017), where TTFields were combined with maintenance temozolomide. In the EF14 study, TTFields-treated patients had a significant improvement in survival compared to patients treated with temozolomide alone (HR, 0.63; p&lt;0.001). Preclinical data has demonstrated that TTFields increase the proportion of glioma cells undergoing cellular death following RT, due to an inhibitory effect on DNA damage repair mechanisms through the homologous recombination pathway. This suggests a radiosensitizing effect for TTFields, potentially increasing the efficacy of RT. The current clinical study was the first to test TTFields when administered concomitant to RT in newly diagnosed glioblastoma patients.
Methods: Ten patients with newly diagnosed glioblastoma were enrolled in this single-arm trial. All had recovered from maximal debulking surgery or biopsy and had Karnofsky performance status ≥70. Patients started TTFields prior to or at the time of RT, and were on stable or decreasing doses of corticosteroids for 7 days prior to enrollment. TTFields (200kHz) were delivered for 18 hours/day with daily removal of the transducer arrays during delivery of RT. Temozolomide was administered at a dose of 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.
Results: Ten patients were enrolled in the trial 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%) were reported to have an adverse event (AE) to date. The most common adverse event reported was TTFields-related skin toxicity, reported in 4 (40%) of the patients enrolled. 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 serious AEs were reported – seizures and general deterioration, both assessed as unrelated to TTFields.
Conclusion: The proportion of patients reported to have TTFields-related skin toxicity (40%) was similar to that reported for the 466 patients treated with TTFields in the phase III study (52%), where patients started TTFields &gt; 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 other therapies. To date, TTFields has demonstrated a high safety profile when combined with other therapies in newly diagnosed GBM. The follow up period on this study is expected to be completed by the end of 2018.
Citation Format: Rachel Grossman, Zvi Ram. Safety of TTFields and radiotherapy (RT) for newly diagnosed glioblastoma: Interim safety results from a pilot study [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 CT086.