Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma

Abstract

IMPORTANCE Tumor-treating fields (TTFields) is an antimitotic treatment modality that interferes with glioblastoma cell division and organelle assembly by delivering low-intensity alternating electric fields to the tumor.OBJECTIVE To investigate whether TTFields improves progression-free and overall survival of patients with glioblastoma, a fatal disease that commonly recurs at the initial tumor site or in the central nervous system. MAIN OUTCOMES AND MEASURESProgression-free survival (tested at α = .046). The secondary end point was overall survival (tested hierarchically at α = .048). Analyses were performed for the intent-to-treat population. Adverse events were compared by group. RESULTSOf the 695 randomized patients (median age, 56 years; IQR, 48-63; 473 men [68%]), 637 (92%) completed the trial. Median progression-free survival from randomization was 6.7 months in the TTFields-temozolomide group and 4.0 months in the temozolomide-alone group (HR, 0.63; 95% CI, 0.52-0.76; P < .001). Median overall survival was 20.9 months in the TTFields-temozolomide group vs 16.0 months in the temozolomide-alone group (HR, 0.63; 95% CI, 0.53-0.76; P < .001). Systemic adverse event frequency was 48% in the TTFields-temozolomide group and 44% in the temozolomide-alone group. Mild to moderate skin toxicity underneath the transducer arrays occurred in 52% of patients who received TTFields-temozolomide vs no patients who received temozolomide alone. CONCLUSIONS AND RELEVANCEIn the final analysis of this randomized clinical trial of patients with glioblastoma who had received standard radiochemotherapy, the addition of TTFields to maintenance temozolomide chemotherapy vs maintenance temozolomide alone, resulted in statistically significant improvement in progression-free survival and overall survival. These results are consistent with the previous interim analysis.TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00916409

Phase 1 lead‐in to a phase 2 factorial study of temozolomide plus memantine, mefloquine, and metformin as postradiation adjuvant therapy for newly diagnosed glioblastoma

“…2 A tumor-treating fields (TTFields) device also was recently approved for use as adjuvant treatment with TMZ after the completion of chemoradiation and reportedly produced a 5-year survival rate of 13%. 3 However, other Cancer February 1, 2019 than radiation, TMZ, and the TTFields device, there are no other effective standard therapies for patients with newly diagnosed GBM.…”

AVNP2 protects against cognitive impairments induced by C6 glioma by suppressing tumour associated inflammation in rats

“…It has attracted the attention of researchers all over the world for its highly aggressive characteristics, high recurrence rate and high mortality (Graus et al, 2013;Tanaka et al, 2013). At present, surgery combined with radiotherapy and chemotherapy is the most common treatment strategy in clinic (Stupp et al, 2017;Okada et al, 2017). However, the tolerance of tumour cells to therapy makes some residual lesions regrow, so the outcomes have not been satisfactory (Stupp et al, 2009).…”

A phase 1 and randomized, placebo‐controlled phase 2 trial of bevacizumab plus dasatinib in patients with recurrent glioblastoma: Alliance/North Central Cancer Treatment Group N0872

“…The standard care for newly diagnosed patients involves maximal surgical resection followed by radiotherapy with concomitant and adjuvant temozolomide; however, the median survival with this approach ranges from 16 to 18 months. 2,3 A high rate of disease recurrence is observed with current therapies for GBM, and various agents have demonstrated limited clinical benefit in this setting. 4 Due to the highly heterogeneous nature of GBM, with several different signaling pathways involved in its pathogenesis, a combination of therapies targeting different pathways may prove to be beneficial.…”