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

e24019 Background: Tumor Treating Fields (TTFields) are an anti-mitotic, regional treatment modality, utilizing low intensity alternating electric fields delivered non-invasively to the tumor using a portable medical device. TTFields are FDA-approved for glioblastoma and malignant pleural mesothelioma. In the EF-14 [NCT00916409] phase 3 GBM study, TTFields significantly extended survival in newly diagnosed GBM when added to maintenance temozolomide (TMZ). Elderly GBM patients usually have worse prognosis and often receive only partial treatment for the disease. The aim of the following post-hoc analysis was to examine the effects of TTFields in the elderly population (≥65 years of age) enrolled in the EF-14 study. Methods: All 134 elderly patients (≥65 years of age) from the EF-14’s intent-to-treat population were included in the analysis, Overall survival (OS) and progression-free survival (PFS), as well as adverse events were compared between the TMZ + TTFields arm and the TMZ alone arm. Results: The median age was 69 (range: 65-83), 69% were male. Median PFS from randomization was 6.5 months versus 3.9 months in the TTFields + TMZ versus TMZ alone arms, respectively (hazard ratio [HR], 0.47 [95%CI 0.30, 0.74] P < 0.0236). Median OS was 17.4 months versus 13.7 months in the TTFields + TMZ versus TMZ alone arm, respectively (HR 0.51 [CI 0.33, 0.77] P < 0.020). Serious adverse events (SAEs) were reported in 39% of patients treated with TTFields + TMZ and in 33% of patients treated with TMZ alone. None of the SAEs were considered related to TTFields. SAEs were considered related to TMZ or to the underlying disease. Grades 1-2 skin AEs were observed in 51% of patients. Conclusions: Consistent with the overall outcome of the EF-14 study, elderly patients treated with TMZ + TTFields showed significantly better OS compared to patients on TMZ alone, and without increase in grade 3-4 toxicity. Clinical trial information: NCT00916409 .

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HOUT-17. ELDERLY PATIENTS >65YEARS OF AGE WITH NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORME GAIN LIFE TIME FROM TREATMENT WITH TUMOR TREATING FIELDS AND TEMOZOLOMIDE

Neuro-Oncology ◽

10.1093/neuonc/noy148.485 ◽

2018 ◽

Vol 20 (suppl_6) ◽

pp. vi116-vi116

Author(s):

Gregory Guzauskas ◽

Bruce CM Wang ◽

Christina Proescholdt

Keyword(s):

Glioblastoma Multiforme ◽

Elderly Patients ◽

Life Time ◽

Newly Diagnosed ◽

Tumor Treating Fields ◽

Newly Diagnosed Glioblastoma

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CTNI-68. EFFICACY OF TTFIELDS IN ELDERLY PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA (GBM) – SUB-GROUP ANALYSIS OF THE EF-14 TRIAL

Neuro-Oncology ◽

10.1093/neuonc/noaa215.234 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii58-ii58

Author(s):

Zvi Ram ◽

Chae-Yong Kim ◽

Jay-Jiguang Zhu

Keyword(s):

Elderly Patients ◽

Electric Fields ◽

Group Analysis ◽

Progression Free Survival ◽

The Elderly ◽

Underlying Disease ◽

Newly Diagnosed ◽

Serious Adverse Events ◽

Tumor Treating Fields ◽

Alternating Electric Fields

Abstract BACKGROUND Tumor Treating Fields (TTFields) are an anti-mitotic, regional treatment that utilizes low intensity alternating electric fields delivered non-invasively to the tumor using a portable medical device. In the EF-14 phase 3 study leading to FDA approval, TTFields significantly extended survival in newly diagnosed GBM when added to maintenance temozolomide (TMZ). Elderly GBM patients usually have worse prognosis and often receive only partial treatment for the disease. This sub-group analysis examined the effects of TTFields in the elderly population (≥65 years of age) enrolled in the EF-14 study. METHODS All 134 elderly patients (≥65 years of age) from the EF-14’s intent-to-treat population were included in the analysis, Overall survival (OS) and progression-free survival (PFS), as well as adverse event frequency and severity were compared between the TMZ/TTFields arm and the TMZ alone arm. RESULTS The median age was 69 (range: 65–83), median KPS was 90%, and 69% were male. Median PFS from randomization was 6.5 months versus 3.9 months in the TMZ/TTFields versus TMZ alone arms, respectively (hazard ratio [HR], 0.47 [95%CI 0.30, 0.74] P< 0.0236). Median OS was 17.4 months versus 13.7 months in the TMZ/TTFields versus TMZ alone arm, respectively (HR 0.51 [CI 0.33, 0.77] P< 0.020). Serious adverse events (SAEs) were reported in 39% of patients treated with TMZ/TTFields and in 33% of patients treated with TMZ alone. None of the SAEs were considered related to TTFields but attributed to TMZ or to the underlying disease. Grades 1–2 skin AEs related to TTFields were observed in 51% of patients. CONCLUSION Consistent with the overall outcome of the EF-14 study, elderly patients treated with TMZ/TTFields showed significantly better OS compared to patients on TMZ alone, and without increase in grade III or IV toxicity.

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Efficacy and Safety of Tumor Treating Fields (TTFields) in Elderly Patients with Newly Diagnosed Glioblastoma: Subgroup Analysis of the Phase 3 EF-14 Clinical Trial

Frontiers in Oncology ◽

10.3389/fonc.2021.671972 ◽

2021 ◽

Vol 11 ◽

Author(s):

Zvi Ram ◽

Chae-Yong Kim ◽

Andreas F. Hottinger ◽

Ahmed Idbaih ◽

Garth Nicholas ◽

...

Keyword(s):

Quality Of Life ◽

Clinical Trial ◽

Elderly Patients ◽

Subgroup Analysis ◽

Newly Diagnosed ◽

Phase 3 ◽

Skin Reactions ◽

Tumor Treating Fields ◽

Grade 3

BackgroundUnderstudied elderly patients comprise a large segment of high-risk patients with glioblastoma (GBM) that are challenging to treat. Tumor Treating Fields (TTFields) is a locoregional, noninvasive, antimitotic therapy delivering low-intensity, intermediate-frequency alternating electric fields to the tumor. In the phase 3 EF-14 clinical trial, TTFields (200 kHz) improved median progression-free survival (PFS) and median overall survival (OS) in patients with newly diagnosed GBM (ndGBM) when added concomitantly to maintenance temozolomide (TMZ). This EF-14 subgroup analysis evaluated the safety and efficacy of TTFields in elderly patients.MethodsAll 134 patients who are ≥65 years of age were included (TTFields/TMZ combination, n=89; TMZ monotherapy, n=45; 2:1 ratio of randomization). PFS and OS were analyzed using Kaplan–Meier methodology (α=0.05). Health-related quality-of-life (HRQoL) was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) quality-of-life questionnaire QLQ-C30 supplemented with the brain tumor module (QLQ-BN20). Adverse events (AEs) were evaluated using Common Terminology Criteria for AEs (CTCAE) v4.0.ResultsThe PFS was 6.5 months in patients randomized to the treatment group with TTFields/TMZ combination versus 3.9 months in patients treated with TMZ monotherapy (HR, 0.47; 95% CI, 0.30–0.74; P<0.0236). The OS was 17.4 months in patients treated with TTFields/TMZ combination versus 13.7 months in patients treated with TMZ monotherapy (HR, 0.51; 95% CI, 0.33–0.77; P<0.0204). Annual survival rates with TTFields/TMZ versus TMZ monotherapy were 39% (95% CI, 29–50%) versus 27% (95% CI, 15–41%; P=0.072) at 2 years, 19% (95% CI, 11–29%) versus 11% (95% CI, 4–23%; P=0.135) at 3 years, and 15% (95% CI, 7–25%) versus 0% at 5 years, respectively. There were no significant differences between groups in the preselected items of HRQoL assessment. Grade ≥3 systemic AEs were 46% in the TTFields/TMZ group versus 40% in the TMZ monotherapy group, without statistically significant difference between the two groups. The only TTFields-related AEs were reversible scalp skin reactions, with grades 1–2 and grade 3 skin reactions reported by 51% and 2% of patients, respectively.ConclusionsCombining TTFields with maintenance TMZ significantly improved PFS and OS in elderly patients with ndGBM in the phase 3 EF-14 clinical trial, without significant increases in systemic toxicity or negatively affecting patient HRQoL. TTFields-related skin AEs were low-grade and manageable.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT00916409, identifier: NCT00916409.

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