Safety and efficacy of tumor treating fields (TTFields) prior and concomitant to radiotherapy in patients with newly diagnosed glioblastoma: Results from PriCoTTF.

person Seid Kebir Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Division of Clinical Neurooncology, University Medicine Essen, University Duisburg-Essen, Essen, Germany info_outline Seid Kebir, Lazaros Lazaridis, Teresa Schmidt, Christoph Oster, Martin Proescholdt, Peter Hau, Anca L. Grosu, Dietmar Krex, Ulrich Sure, Björn Scheffler, Christoph Kleinschnitz, Christoph Pöttgen, Martin Stuschke, Martin Glas

Authors person Seid Kebir Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Division of Clinical Neurooncology, University Medicine Essen, University Duisburg-Essen, Essen, Germany info_outline Seid Kebir, Lazaros Lazaridis, Teresa Schmidt, Christoph Oster, Martin Proescholdt, Peter Hau, Anca L. Grosu, Dietmar Krex, Ulrich Sure, Björn Scheffler, Christoph Kleinschnitz, Christoph Pöttgen, Martin Stuschke, Martin Glas Organizations Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Division of Clinical Neurooncology, University Medicine Essen, University Duisburg-Essen, Essen, Germany, Department of Neurosurgery, University Hospital Regensburg, Regensburg, Germany, Department of Radiation Oncology, Medical Center - University of Freiburg, Freiburg, Germany, Department of Neurosurgery, Carl Gustav Carus University Hospital Dresden, Dresden, Germany, Department of Neurosurgery and Spine Surgery, University Medicine Essen, University Duisburg-Essen, Essen, Germany, DKFZ-Division Translational Neurooncology at the West German Cancer Center (WTZ), DKTK Partner Site, University Medicine Essen; German Cancer Consortium (DKTK), Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany, Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (CTNBS), Division of Clinical Neurooncology, University Medicine Essen, University Duisburg-Essen, Essen, Germany, Department of Radiotherapy, University Medicine Essen, University Duisburg-Essen, Essen, Germany, Division of Clinical Neurooncology, Department of Neurology, University Hospital Essen, University Duisburg-Essen, West German Cancer Center (WTZ) and German Cancer Consortium, Partner Site, Essen, Germany Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Novocure Ltd Background: Tumor Treating Fields (TTFields) therapy is a locoregional, antimitotic cancer modality that utilizes electric fields delivered noninvasively to the tumor region using arrays. Preclinical findings have demonstrated that TTFields have an enhanced inhibitory effect on glioblastoma (GBM) cell proliferation when used concomitantly with radiotherapy (RT). These results provided the rationale for the phase 1/2 PriCoTTF study that investigated the safety and efficacy of TTFields therapy initiated prior and concomitant to radio-chemotherapy in adult patients with newly diagnosed (nd)GBM. Methods: TTFields therapy was initiated following surgery and continued concomitant with radio-chemotherapy and adjuvant chemotherapy for a total of approximately 9 months. TTFields rechallenge was permitted upon GBM recurrence. RT was conducted with arrays placed on the patients’ scalp. The primary endpoint was safety and tolerability gauged by a series of pre-selected treatment-limiting toxicities (TLTs). Results: The baseline characteristics of 33 patients enrolled to date were typical for GBM, except for a small proportion of patients with gross total resection (22.5%). The frequency of adverse events (AEs) grade ≥ 3 was comparable to other studies in GBM. Of note, grade ≥ 3 skin AEs only occurred in 2 patients (6%) and no patients developed a TLT. The median duration of TTFields therapy was 8.4 months. Median overall survival (OS) was not reached (48% of events had occurred), which precluded conclusions regarding efficacy. However, notably, multivariable Cox regression found that OS was independently associated with the number of days patients achieved > 23 h TTFields therapy (HR 0.96, 95% CI 0.93–0.99, P = 0.008). Conclusions: The PriCoTTF study met its primary endpoint by finding that TTFields therapy concomitant with RT was well tolerated in patients with ndGBM. This included that high-grade skin toxicities were rare. Longer follow up is needed to estimate the efficacy of TTFields therapy in this setting, and will need to consider the relatively low overall duration of TTFields therapy and proportion of patients who received GTR.