IQWiG released a rapid report on tumor-treating field therapy in glioblastoma in Germany

Glioblastoma is an aggressive brain tumor with a low survival rate, usually occurring in late adulthood. The standard treatment consists of surgery, followed by radiation and chemotherapy. The Institute for Quality and Efficiency in Health Care (IQWiG) has examined possible benefits of tumor-treating field (TTF) therapy - new treatment based on electrostimulation in patients with glioblastoma.

TTF therapy is a non-invasive treatment method that aims to inhibit tumor growth with the help of alternating electrical fields. Electrostimulation takes place via ceramic gel pads placed on the head. In order a direct skin contact to be possible, the scalp must be shaved. The electricity comes from a portable field generator. The patients can use this therapy themselves, for 18 hours a day, if possible.

The G-BA commissioned IQWiG to prepare the report using an accelerated procedure as a so-called rapid report in November 2018 after the results of a randomized controlled trial study (EF-14 trial) was published. Intermediates were therefore not published and not put to the hearing.

The identified EF-14 study is a multi-center randomized study with 83 centers in North America, Europe, South Korea, and Israel. 695 patients with newly diagnosed glioblastoma participated in the study. All patients received as much resection or biopsy as possible at the beginning of the first-line therapy and subsequent radiotherapy combined with temozolomide. The randomization was done before the subsequent maintenance phase the first group received adjuvant chemotherapy with temozolomide in combination with TTF (hereafter called temozolomide + TTF; n=466) and the second group received 6 cycles of temozolomide as monotherapy (hereafter called temozolomide; n=229).

Results:

• Survival: there was a statistically significant difference in favor of temozolomide + TTF towards temozolomide at the end of the study: HR=0.63, 95% CI [0.53; 0.76]. While the patients in this group survived a median of 20.9 months from baseline (95% CI [19.1; 22.6]), there were only 16.0 months in the comparison group (95% CI [13, 9, 18, 2]). This effect was confirmed by a planned interim analysis after the first 315 patients had been followed for at least 18 months. Thus, there is an indication of a higher benefit of the additional treatment with TTF for mortality compared to the current standard treatment with temozolomide
• Symptoms: there was no statistically significant difference between the treatment groups for the outcome "pain and weakness of the legs" as measured by the respective symptom scales of the EORTC QLQ-C30 and EORTC QLQ-BN20. For the outcome "itching of the skin" as measured by the EORTC QLQ-BN-20 symptom scale, there was a statistically significant difference to the disadvantage of temozolomide + TTF versus temozolomide at 3 months, but not at 12 months. Thus, for the endpoints of pain and weakness of the legs, there is no hint of a more significant benefit or harm of temozolomide + TTF compared with temozolomide. There was a hint of the increased harm from temozolomide + TTF versus temozolomide for the skin itching endpoint, which is based on early-stage data
• Cognition: the cognitive performance score measured by the MiniMental Status Test (MMST) showed a statistically significant difference in favor of temozolomide + TTF versus temozolomide: HR=0.81, 95% CI [0.68; 0.97], confirming a greater benefit of temozolomide + TTF over temozolomide for this indicator
• Daily life activities: there was a statistically significant difference in favor of temozolomide + TTF versus temozolomide for the outcome "activities of daily life" measured by the Karnofsky index: HR=0.84, 95% CI [0.71; 0.99], confirming a more significant benefit of temozolomide + TTF over temozolomide for this indicator
• Adverse effects/events: there were no statistically significant differences between the treatment groups for the outcomes "serious adverse events (AEs)," "severe AEs" and "discontinuation due to AEs" in general. When looking at the individual cases of serious AEs, there was a statistically significant difference to the disadvantage of temozolomide + TTF versus temozolomide (OR=2.09, 95%CI [1.03, 4.25]). There was no statistically significant difference between the treatment groups in the specific serious AEs investigated: vomiting, balance disorders, convulsions, headache, visual field limitations, status epilepticus, and psychiatric disorders. Overall, there was a hint of greater harm from temozolomide + TTF compared to temozolomide
• Quality of life: for the outcome "health-related quality of life" no statistically significant difference was identified between the treatment groups. Thus, there was no evidence of any more substantial benefit or harm from temozolomide + TTF compared to temozolomide

Therefore, IQWiG sees evidence of a greater benefit of TTF compared to standard therapy.

The full details in German can be found here.

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