334PD - Tumor Treating Fields (TTFields) – A novel cancer treatment modality: Translating preclinical evidence and engineering into a survival benefit with...

Date 09 September 2017
Event ESMO 2017 Congress
Session CNS tumours
Topics Central Nervous System Malignancies
Presenter Roger Stupp
Citation Annals of Oncology (2017) 28 (suppl_5): v109-v121. 10.1093/annonc/mdx366
Authors R. Stupp1, M. Taphoorn2, L. Dirven3, S. Taillibert4, J. Honnorat5, T. Chen6, J. Sroubek7, S.H. Paek8, J. Bruna Escuder9, J. Easaw10, C. David11, C.Y. Kim12, R. Desai13, Y. Kew14, A. Olivi15, A. Hottinger16, E.D. Kirson17, G. Lavy-Shahaf17, M.E. Hegi18, Z. Ram19
  • 1Robert H. Lurie Comprehensive Cancer Center Of Northwestern University, Northwestern University Feinberg School of Medicine, 60611 - Chicago/US
  • 2Neurology, Leiden University Medical Center, 2501 CK - The Hague/NL
  • 3Department Of Neurology, Leiden University Medical Center, Leiden/NL
  • 4Neuro-oncology, Hôpital Universitaire Pitié-Salpêtrière, Paris/FR
  • 5Neuro-oncology, Hospices Civils de Lyon, University Claude Bernard Lyon, Lyon/FR
  • 6Neurosurgery, University of Southern California, Los Angeles/US
  • 7Neurosurgery, Na Homolce Hospital, Prague/CZ
  • 8Neurosurgery, Seoul National University Hospital (SNUH), Seoul/KR
  • 9Department Of Neurology, Bellvitge Hospital Universitari, Barcelona/ES
  • 10Medical Oncology, Tom Baker Cancer Centre, Calgary/CA
  • 11Neurosurgery, Lahey Clinic, Burlington/US
  • 12Neurosurgery, Seoul National University Bundang Hospital, Bundang/KR
  • 13Neurosurgery And Spine Assoc., Maine Medical Center (MMC), Scarborough/US
  • 14Neurology, Methodist Hospital, Houston/US
  • 15Neurosurgery, The Johns Hopkins Hospital, Baltimore/US
  • 16Medical Oncology, Centre Hospitalier Universitaire Vaudois - CHUV, 1011 - Lausanne/CH
  • 17Research And Development, Novocure, Haifa/IL
  • 18Dept. Of Neurosurgery Bh-19/110, Centre Hospitalier Universitaire Vaudois - CHUV, 1011 - Lausanne/CH
  • 19Neurosurgery, Tel Aviv Medical Center, Tel Aviv/IL

Abstract

Background

TTFields is a novel cancer treatment modality using a patient-operated home-use device delivering alternating electrical fields interfering with cell division and selectively disrupting mitosis. Clinical trials are ongoing in various solid tumors and phase 3 trials in glioblastoma (GBM) were recently concluded.

Methods

TTFields were tested in two large phase 3 trials in patients with recurrent (EF-11; n = 237) and newly diagnosed GBM (EF-14; n = 695). Both trials aimed at improving overall survival (OS) with TTFields and included quality of life (QOL) using the EORTC QLQ C-30 with brain cancer module (BN-20) as a secondary endpoint.

Results

In recurrent GBM, TTFields monotherapy was compared to best physician’s choice chemotherapy and failed to demonstrate a superior OS. However, improved response rate (14% vs 9.6%) and a comparable OS (HR 0.86 [CI 0.66–1.12]; p = 0.27) suggested clinical activity. The absence of systemic toxicity was favorably noted by many patients. In newly diagnosed GBM, TTFields was added to standard adjuvant TMZ chemotherapy and led to a significant prolongation of OS (HR 0.63 [CI 0.53-0.76]; p = 0.000059), without added systemic toxicity. OS was extended in all patient subgroups tested including MGMT unmethylated tumors and elderly GBM. More TTFields patients reported stable or improved scores on global health status, pain, physical functioning and leg weakness (all p≤.01). Deterioration free survival was significantly longer with TTFields for global health, physical and emotional functioning, pain and leg weakness (all p

Conclusions

TTFields are an effective treatment for GBM with a novel mechanism of action and unique delivery method. Patients become rapidly independent in handling the device allowing patients to control their treatment at home with stable or improved QOL. The significant survival benefit observed in GBM serves as a proof of principle and establishes this novel modality as a promising anti-cancer therapy in a variety of solid tumors. Due to the lack of overlapping toxicities it can be easily combined with established treatments.

Clinical trial identification

NCT#00379470 and NCT#00916409

Legal entity responsible for the study

Novocure Ltd.

Funding

Novocure Ltd.

Disclosure

R. Stupp: Travel funding from Novocure Ltd. The institutions received research funding for the phase 3 trials mentioned in the abstract from Novocure Ltd. S. Taillibert: The institution received funding for the two phase 3 trials in this abstract from Novocure Ltd. J. Honnorat: Participated in a Novocure sponsored advisory board. The institution received funding for the two phase 3 trials in this abstract from Novocure Ltd. T. Chen: The institution received research funding for the phase 3 trial in newly diagnosed GBM from Novocure Ltd. J. Sroubek: The institution received research funding for the phase 3 trials in this abstract from Novocure Ltd. S.H. Paek, J. Bruna Escuder, J. Easaw, C.Y. Kim: The institution received research funding from Novocure Ltd. for the phase 3 trial in ndGBM. C. David: The institution received research funding from Novocure Ltd. for the ndGBM phase 3 trial. R. Desai: The institution received research funding for the study from Novocure. Y. Kew: The institution received research funding for the phase 3 study from Novocure. A. Olivi: The institution received research funding for the EF14 study from Novocure. A. Hottinger: Honoraria for advisory boards from Novocure. The institution received research funding for both phase 3 trials mentioned in the abstract from Novocure). E.D. Kirson: Employee of Novocure and stock owner. G. Lavy-Shahaf: Employee of Novocure. M.E. Hegi: The institution received research funding from Novocure for performing genetic analyses of the tissue samples in the study. Z. Ram: Paid consultant to Novocure Ltd. All other authors have declared no conflicts of interest.