ACTR-27. COMPLIANCE AND TREATMENT DURATION PREDICT SURVIVAL IN A PHASE 3 EF-14 TRIAL OF TUMOR TREATING FIELDS WITH TEMOZOLOMIDE IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

Abstract Introduction: Tumor-treating fields (TTF) is an established modality for glioblastoma (GBM) treatment administered through the portable Optune system. The efficacy of Optune for newly diagnosed GBM was demonstrated in the EF-14 phase 3 trial. Although TTF is now included as part of initial treatment in the Japan GBM guideline, it is not yet a standard therapy because the procedures are cumbersome and may impose unnecessary psychological burdens on patients with dire prognoses. In our institution, TTF therapy has been offered as a treatment option for GBM patients since January 2018. This report summarizes our initial experience with this novel treatment. Methods: The medical records of the first eight patients with newly diagnosed glioblastoma who underwent TTF were retrospectively reviewed. Results: The eight patients with newly diagnosed glioblastoma treated with TTF comprised five men and three women (median age, 68 years; range 34–83 years). Nine patients were offered TTF therapy, but one declined because of the need for a shaved head. The patients continued TTF for 1–7 months, without major complications. Skin reaction was the most prevalent adverse event (n = 5). One patient could not continue TTF treatment after femoral neck fracture due to the weight of the mobile battery. One patient who did not have a helper at home received TTF treatment from a nurse visiting his home. Conclusions: Patients should be provided with information on TTF, such as the timing of informed consent during and after chemoradiotherapy, to help them better understand this new modality and secure their consent.

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Efficacy Of Tumor Treating Fields (TTFields) In Elderly Patients With Newly Diagnosed Glioblastoma (GBM): Sub-Group Analysis Of The Phase 3 EF-14 Trial

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2020.07.124 ◽

2020 ◽

Vol 108 (3) ◽

pp. e730-e731

Author(s):

Z. Ram ◽

J.J. Zhu

Keyword(s):

Elderly Patients ◽

Group Analysis ◽

Newly Diagnosed ◽

Phase 3 ◽

Tumor Treating Fields ◽

Newly Diagnosed Glioblastoma

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NCOG-05. TIME TO FUNCTIONAL AND COGNITIVE DECLINE IN A PHASE 3 TRIAL OF TUMOR TREATING FIELDS WITH TEMOZOLOMIDE VERSUS TEMOZOLOMIDE ALONE IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

Neuro-Oncology ◽

10.1093/neuonc/nox168.566 ◽

2017 ◽

Vol 19 (suppl_6) ◽

pp. vi138-vi138

Author(s):

Garth A Nicholas ◽

Holger Hirte ◽

Jacob Easaw ◽

Thierry Muanza ◽

David Roberge ◽

...

Keyword(s):

Cognitive Decline ◽

Newly Diagnosed ◽

Phase 3 ◽

Tumor Treating Fields ◽

Newly Diagnosed Glioblastoma

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CTNI-74. PHASE 3 TRIDENT TRIAL: CONCOMITANT RADIATION THERAPY (RT) AND TEMOZOLOMIDE +/- TUMOR TREATING FIELDS (TTFIELDS) IN NEWLY DIAGNOSED GLIOBLASTOMA

Neuro-Oncology ◽

10.1093/neuonc/noaa215.240 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii59-ii60

Author(s):

Wenyin Shi ◽

Lawrence Kleinberg ◽

Suriya A Jeyapalan ◽

Samuel Goldlust ◽

Seema Nagpal ◽

...

Keyword(s):

Radiation Therapy ◽

Progression Free Survival ◽

Phase Iii ◽

Type I ◽

Newly Diagnosed ◽

Phase 3 ◽

Free Survival ◽

Tumor Treating Fields ◽

Newly Diagnosed Glioblastoma

Abstract BACKGROUND Tumor treating fields (TTFields) is a non-invasive, regional antimitotic treatment approved as a standard-of-care for newly diagnosed glioblastoma (ndGBM). In the EF-14 Phase 3 trial, TTFields (200 kHz) plus temozolomide (TMZ) significantly increased survival of ndGBM patients without increasing systemic toxicity. TTFields-related AEs were mainly skin AEs. In preclinical models, TTFields increase the therapeutic effects of radiation therapy (RT). A pilot study showed that TTFields concomitant with RT and TMZ is well tolerated. The benefit of concomitant TTFields with RT and TMZ will be tested in the TRIDENT trial. METHODS TRIDENT is an international phase III randomized trial comparing standard RT with TMZ vs the triple combination of RT/TMZ with concomitant TTFields. RT is delivered through the TTFields arrays. Patients in both arms will receive maintenance TTFields/TMZ. TTFields (200 KHz) will be delivered >18 hours/day using Optune. Patients will continue TTFields treatment until second recurrence. Patients with pathologically confirmed ndGBM, ≥ 18 years, KPS ≥ 70, either sex, post-surgery or biopsy, and amenable for RT/TMZ therapy will be stratified by extent of resection and MGMT promoter methylation status. The primary endpoint is overall survival (OS). Secondary end points: progression free survival (PFS; RANO), 1- and 2-year survival rates, overall radiological response (ORR; RANO), progression-free survival (PFS6M, PF12M, PFS2Y); severity and frequency of AEs (CTCAE V5.0); pathological changes in resected GBM tumors post treatment; quality of life (EORTC QLQ-C30); and correlation of OS to TTFields compliance. The hypothesis is that concomitant TTFields/RT/TMZ will significantly improve OS versus RT/TMZ. Sample size (N=950; 475/arm) will detect a HR< 0.8 with 5% type I error. Survival will be measured from the time of randomization until date of death. At the time of analysis, patients lost to follow-up or still on protocol follow-up will be censored at the last date known to be alive.

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CTNI-09. TRIDENT PHASE 3 TRIAL (EF-32): FIRST-LINE TUMOR TREATING FIELDS (TTFields; 200 KHZ) CONCOMITANT WITH CHEMO-RADIATION, FOLLOWED BY MAINTENANCE TTFIELDS/TEMOZOLOMIDE IN NEWLY-DIAGNOSED GLIOBLASTOMA

Neuro-Oncology ◽

10.1093/neuonc/noab196.234 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi60-vi61

Author(s):

Wenyin Shi ◽

Lawrence Kleinberg ◽

Suriya Jeyapalan ◽

Samuel Goldlust ◽

Seema Nagpal ◽

...

Keyword(s):

Methylation Status ◽

Type I ◽

Newly Diagnosed ◽

Triple Combination ◽

First Line ◽

Phase 3 ◽

Pivotal Phase ◽

Tumor Treating Fields ◽

Post Surgery ◽

Newly Diagnosed Glioblastoma

Abstract INTRODUCTION Tumor Treating Fields (TTFields; 200 kHz; non-invasive, loco-regional antimitotic treatment) is approved for newly-diagnosed glioblastoma (ndGBM). In the Phase 3 EF-14 trial, post-surgical radiotherapy/temozolomide, followed by maintenance TTFields/temozolomide significantly increased overall survival (OS) and progression-free survival (PFS) in patients with ndGBM versus TMZ alone. Addition of maintenance TTFields did not increase systemic toxicity; and related adverse events (AEs) were mainly dermatological. In preclinical models, addition of TTFields increased the benefit of radiotherapy. Two pilot studies showed that TTFields concomitant with radiotherapy/temozolomide is feasible and well-tolerated. The benefit of TTFields concomitant with radiotherapy/temozolomide will be investigated in the TRIDENT trial. METHODS TRIDENT (EF-32; NCT04471844) is an international, pivotal, phase 3 randomized trial comparing triple-combination of TTFields/radiotherapy/temozolomide versus standard radiotherapy/temozolomide. Patients in both arms will receive maintenance TTFields/TMZ. Arrays of the Optune® System will be used to deliver TTFields (200 KHz) for ≥18 hours/day concomitant with radiotherapy. TTFields treatment will be continued until second disease progression (RANO) or 24 months, whichever occurs first. Patients with pathologically-confirmed ndGBM, ≥ 18 years of age (≥ 22 years of age; US), KPS ≥ 70, post-surgery/biopsy, and amenable for radiotherapy/temozolomide will be stratified by extent-of-resection and MGMT promoter methylation status. The primary endpoint is median OS. Secondary endpoints include median PFS (RANO), 1-year and 2-year survival rates, overall radiological response (ORR; RANO), PFS (PFS-6M, PFS-12M, PFS-2Y), severity and frequency of AEs (CTCAE V5.0), pathological post-treatment changes in resected GBM tumors, quality-of-life (EORTC QLQ-C30), and OS correlation to TTFields duration-of-usage. The hypothesis is that first-line TTFields/RT/TMZ triple-combination will significantly improve OS compared to radiotherapy/temozolomide; each followed by maintenance TTFields/temozolomide. Sample size (N=950; 475/arm) was powered for a HR < 0.8 with 5% type I error. Survival will be measured from time-of-randomization. The TRIDENT trial is currently enrolling patients. RESULTS/CONCLUSIONS N/A TiP.

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