AACR 2019: Spotlight on tumour treating fields
Tumour treating fields (TTFields), alternating electric fields delivered via transducer arrays placed on the scalp, have emerged as a new modality of treatment for glioblastoma (GBM), with studies showing improved survival in patients with newly diagnosed or recurrent disease. New data presented at the American Association for Cancer Research (AACR) Annual Meeting 2019 held in Atlanta, Georgia, US, provide insights into its use in GBM treatment.
Increasing dose at tumour bed improves survival in newly diagnosed GBM
Increasing the dose of TTFields at the tumour bed can improve overall survival (OS) and progression-free survival (PFS) in patients with newly diagnosed GBM, according to an analysis of the phase III EF-14 trial. [Ballo MT, et al, AACR 2019, abstract CT204 / 18]
The simulation-based analysis showed a patient-level dose response to TTFields therapy, with an average local minimum dose density (LMiDD) of ≥0.77 MmW/cm3 being associated with significant improvements in OS (25.2 months vs 20.4 months for LMiDD <0.77 MmW/cm3; hazard ratio [HR], 0.611; p=0.003) and PFS (8.5 months vs 6.7 months; HR, 0.699; p=0.02).
In addition, an average TTFields intensity of ≥1.06 V/cm was associated with longer OS (24.3 months vs 21.6 months for <1.06 V/cm; hazard ratio [HR], 0.705; p =0.03) and PFS (8.1 months vs 7.9 months; HR, 0.721; p=0.03).
The analysis included 214 patients treated with TTFields for ≥2 months who had MRI images of sufficient quality for the creation of realistic computational head models. LMiDD was defined as the product of TTFields power loss density and average patient compliance.
TTFields plus RT and temozolomide: Promising in newly diagnosed GBM
Concomitant use of TTFields, radiotherapy (RT) and temozolomide (TMZ) has shown promising results in patients with newly diagnosed GBM in a single-centre pilot study.
Among 10 patients (median age, 59 years; median Karnofsky performance status, 80) treated with this approach, median PFS was 10.5 months, while median OS was not yet reached. [Grossman R, et al, AACR 2019, abstract CT008 / 3]
Adverse events (AEs) were reported in six patients. The most common AE was TTFields-related grade 1/2 skin toxicity, reported in four patients. Two patients reported serious AEs (seizures and general deterioration), which were considered to be unrelated to TTFields.
No other TTFields-related toxicities were reported. There was also no increase in RT- or TMZ-related toxicities with the concomitant use of TTFields.
In the study, TTFields therapy was delivered for ≥18 hours/day, with transducer arrays removed during delivery of RT. Following completion of concomitant TTFields/RT/TMZ therapy, maintenance TTFields and TMZ were given for up to 24 months.
Based on these safety and preliminary efficacy results, a phase II randomized trial has been initiated to further evaluate the efficacy of concomitant TTFields/RT/TMZ therapy in patients with newly diagnosed GBM (n=60).
TTFields therapy alters progression patterns in GBM
An imaging analysis of the phase III EF-14 trial suggests that TTFields therapy, used in combination with temozolomide (TMZ), has a substantial impact on GBM growth patterns and rate. [Jeyapalan S, et al, AACR 2019, abstract CT205 / 19]
The analysis included patients on treatment for ≥2 months who showed radiological progression (treatment arm, n=280/466; control arm, n=122/229). Results showed that non-local (distal or local and distal combined) progression was numerically more common in the treatment arm vs control arm (69/280 vs 23/122; p<0.15).
At progression, distal lesions were more distant from the original lesions among patients in the treatment arm. Infratentorial progression was observed in 10 patients (4 percent) in the treatment arm vs none of the patients in the control arm (p<0.002).
Mean tumour growth rate was found to be higher in the control vs treatment arm (0.078 mL/day vs 0.036 mL/day; p<0.05).
According to the investigators, the results validate the local efficacy of TTFields in increasing local control of tumour growth, highlighting the need for adaptive treatment after GBM progression. “Further studies are needed to elucidate the association between progression and TTFields dose distributions,” they suggested.
High compliance with TTFields in high-grade glioma patients
Compliance with TTFields therapy is high among patients with high-grade newly diagnosed or recurrent glioma, a single-centre study has shown. [Hagemann C, et al, AACR 2019, abstract LB-155 / 13]
The study included 36 patients at a median age of 53.5 years when TTFields therapy was initiated. Twenty-eight patients were diagnosed with GBM (newly diagnosed, n=21; recurrent, n=7; male:female, 1:1.15), while eight were diagnosed with astrocytoma WHO ֯III.
Among patients with newly diagnosed GBM, median TTFields therapy duration was 6.9 months at the time of data cut-off. The median compliance/usage rate was 84.2 percent, with no significant difference between males (81.1 percent) and females (84.3 percent).
In patients with recurrent GBM, the median compliance rate was 71.1 percent, which was not significantly different compared with patients with newly diagnosed GBM.
In patients with astrocytoma WHO ֯III, the compliance rate was 84.5 percent.
These high compliance rates support recommendations for the use of TTFields in all eligible patients with high-grade glioma, the investigators concluded.
In a recently published subgroup analysis of the phase III EF-14 study, a monthly TTFields compliance rate of ≥75 percent was found to be an independent predictor of OS in patients with newly diagnosed GBM. [J Neurooncol 2019;141:467-473]