TTFields plus TMZ effective for newly diagnosed GBM in elderly
Consistent with the overall outcome of the phase III EF-14 study, elderly patients with newly diagnosed glioblastoma multiforme (GBM) treated with tumour-treating fields (TTFields) and temozolomide (TMZ) showed significantly better overall survival (OS) vs patients on TMZ alone, according to a post-hoc analysis presented at the American Association for cancer Research (AACR) 2020 Virtual Annual Meeting II.
TTFields are an anti-mitotic, regional treatment modality that utilizes low-intensity alternating electric fields delivered non-invasively to the tumour via a portable medical device. In the phase III EF-14 study, which led to US FDA approval, TTFields significantly extended survival of patients with newly diagnosed GBM when added to maintenance TMZ. [JAMA 2017;318:2306-2316]
Elderly GBM patients usually have worse prognosis and often only receive partial treatment for their disease. The aim of the post-hoc analysis was to examine the effects of TTFields in the elderly population (≥65 years of age) enrolled in the EF-14 study. The trial enrolled 134 elderly patients (median age, 69 years; male, 69 percent; median Karnofsky performance status, 90 percent) who were randomized 2:1 to receive TTFields plus TMZ or TMZ alone. All elderly patients were included in the current analysis. [Ram Z et Zhu JJ, AACR 2020 Virtual Meeting II, abstract 10636]
Median OS in the TTFields plus TMZ group was 17.4 months vs 13.7 months in the TMZ only group (hazard ratio [HR], 0.51; 95 percent confidence interval [CI], 0.33 to 0.77; p<0.020). Median PFS was 6.5 months with TTFields plus TMZ vs 3.9 months with TMZ alone (HR, 0.47; 95 percent CI, 0.30 to 0.74; p<0.0236).
While grade 1/2 skin adverse events (AEs) were observed in 51 percent of patients on TTFields, its addition to TMZ did not show a significant increase in systemic AEs vs TMZ alone (46 percent vs 40 percent; p=0.3518). “The serious AEs reported in 39 percent of patients on TTFields plus TMZ and in 33 percent of patients on TMZ alone were considered not related to TTFields, but rather to TMZ or the underlying disease,” wrote the researchers.
“The improvements in survival – an absolute increase of 2.6 months in PFS and 3.7 months in OS – with the addition of TTFields observed in this elderly subgroup indicate that adding TTFields to TMZ is an effective and safe strategy for elderly patients with newly diagnosed GBM,” they commented.
Mean compliance with TTFields (≥18 hours/day) was seen in 57 percent of patients during the first 3 months of treatment and was linked to better outcomes. The OS of patients who wore the TTFields device for ≥18 hours/day vs ≤18 hours/day was 21.3 months vs 12.5 months (p=0.0076).
At 1 year, the PFS rate was 75 percent for TTFields plus TMZ vs 52.4 percent for TMZ alone (p=0.013). The respective 2-year and 3-year PFS rates were 47.3 percent vs 30.5 percent and 27.1 percent vs 12.3 percent, respectively, but the differences between treatment arms did not reach statistical significance.