Tumor-treating fields plus chemotherapy versus chemotherapy alone for glioblastoma at first recurrence: a post hoc analysis of the EF-14 trial

CNS Oncol. 2017 Jul;6(3):185-193. doi: 10.2217/cns-2016-0049. Epub 2017 Apr 12.


Background: This post hoc analysis of the EF-14 trial (NCT00916409) of tumor-treating fields (TTFields) plus temozolomide versus temozolomide alone in newly diagnosed glioblastoma compared the efficacy of TTFields plus chemotherapy (physician's choice) versus chemotherapy alone after first recurrence.

Methods: Patients on TTFields plus temozolomide continued TTFields plus second-line chemotherapy after first recurrence. Some patients on temozolomide alone crossed over after approval of TTFields for recurrent GBM. The primary efficacy outcome was overall survival (OS).

Results: After disease progression, 131 patients received TTFields plus chemotherapy and 73 chemotherapy alone. Thirteen patients in the original temozolomide-alone group crossed over to receive TTFields plus chemotherapy after disease progression, resulting in 144 patients receiving TTFields plus chemotherapy and 60 chemotherapy alone. Median follow-up was 12.6 months. Bevacizumab, alone or with cytotoxic chemotherapy, was the most frequent treatment. Median OS in the TTFields plus chemotherapy group was significantly longer versus chemotherapy alone (11.8 vs 9.2 months; HR: 0.70; 95% CI, 0.48-1.00; p=0.049). TTFields showed a low toxicity safety profile, as previously reported, with no grade 3/4 device-related adverse events.

Conclusion: TTFields plus chemotherapy after first disease recurrence on TTFields plus temozolomide or temozolomide alone prolonged OS in patients in the EF-14 trial.

Keywords: TTFields; bevacizumab; disease recurrence; glioblastoma; overall survival; second-line chemotherapy.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aftercare
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Antineoplastic Agents, Immunological / therapeutic use
  • Bevacizumab / therapeutic use
  • Brain Neoplasms / therapy*
  • Combined Modality Therapy
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / therapeutic use
  • Electric Stimulation Therapy*
  • Female
  • Glioblastoma / therapy*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / therapy*
  • Neurosurgical Procedures
  • Radiotherapy
  • Survival Analysis
  • Temozolomide
  • Treatment Outcome
  • Young Adult


  • Antineoplastic Agents, Alkylating
  • Antineoplastic Agents, Immunological
  • Bevacizumab
  • Dacarbazine
  • Temozolomide

Associated data

  • ClinicalTrials.gov/NCT00916409