Novo TTF( Optune) was FDA approved in April 2011 under orphan disease designation for recurrent glioblastoma.TTF therapy has been shown in vitro and in vivo to effectively inhibit tumor growth by inducing cell death. TTF takes advantage of the electrical characteristics, geometrical shape and replication rate of dividing cancer cells – all of which makes them susceptible to the effects of alternating electric fields. TTF therapy is delivered using non-invasive, insulated transducer arrays that are placed directly on the skin in the region of the tumor. TTF therapy does not deliver any electric current to the tissue; it does not stimulate nerves or muscles or heat the tissue. It creates an artificial, alternating electric field within the tumor which disrupts cancer cell division and can cause complete destruction of the dividing cancer cells.
In a randomized Phase III clinical trial, the NovoTTF-100A device has at least equivalent efficacy, and with fewer treatment-related side effects, to the salvage cytotoxic chemotherapies that have established efficacy against recurrent glioblastoma. The supporting trial subgroup analysis was presented as abstract Number: NO-55 entitled, Subgroup and quality of life analyses of the phase III clinical trial of NovoTTF-100 versus best standard chemotherapy for recurrent glioblastoma at Society of Neuro-oncology on September 19, 2010.
The most recent update of the study above as recently published (2014) says: “Treatment with NovoTTF-100A System, as prescribed in the neuro-oncology clinical practice to patients with recurrent glioblastoma offers favorable outcomes when compared to historical data. Patient compliance with the prescribed use of the system is high and positively correlates with improved survival. Bevacizumab naïve patients benefit more while patients with poor KPS and multiple prior recurrences benefit less from this treatment. NovoTTF-100A System is well tolerated and has no new unexpected toxicities since its introduction to clinical practice.”.
The next advance was in patients who recieved Optune adjuvantly. Optune was studied in the EF-14 trial, a prospective, international, multicenter, open-label, randomized, controlled, phase 3 trial in newly diagnosed GBM patients comparing Optune + TMZ with TMZ alone (N=700). The prespecified interim analysis occurred when the first 315 patients completed 18 months of follow-up.
Patients’ quality of life, cognitive function, and ability to perform activities of daily living did not significantly decline with the use of Optune + TMZ in patients for whom 12 months of QoL data were available. Median OS significantly extended by 4.9 months: 20.9 months median OS with Optune + TMZ vs 16.0 months with TMZ alone (P=0.00006).
The updated NCCN Clinical Practice Guidelines In Oncology (NCCN Guidelines®) for Central Nervous System Cancers now include alternating electric field therapy (Optune) in combination with temozolomide (TMZ) following standard brain radiation therapy with concurrent TMZ as a Category 2A recommended postoperative adjuvant treatment option for patients with newly diagnosed supratentorial glioblastoma (GBM). Optune is intended as a treatment for adult patients (22 years of age or older) with histologically-confirmed glioblastoma multiforme (GBM).
Optune with temozolomide is indicated for the treatment of adult patients with newly diagnosed, supratentorial glioblastoma following maximal debulking surgery, and completion of radiation therapy together with concomitant standard of care chemotherapy.
Stupp R, Kanner A, Engelhard H et al. A prospective, randomized, open-label, Phase III clinical of NovoTTF-100A versus best standard of care chemotherapy in patients with recurrent glioblastoma. J. Clin. Oncol. 28(18), LBA2007 (2011).
M.M.Mrugala et al, Alternating electric fields therapy for recurrent glioblastoma – NovoTTF-100A system: Updated outcomes and toxicity based on the analysis of patient. Annals of Oncology (2014) 25 (suppl_4): iv137-iv145.
Stupp et al. “NovoTTF-100A versus physician’s choice chemotherapy in recurrent glioblastoma: A randomised phase III trial of a novel treatment modality.” European Journal of Cancer (2012)
Ram Z, Gutin PH, Stupp R. Subgroup and quality of life analyses of the phase III clinical trial of NovoTTFields-100A versus best standard chemotherapy for recurrent glioblastoma. Neuro Oncol. 2010;12(Suppl 4):iv36-iv57.
Pless M,BetticherDC, Buess M, et al. A phase II study of tumor-treating fields (TTFields) in combination with pemetrexed for advanced non-small cell lung cancer (NSCLC). ESMO; 2010. Abstract 371PD.
Pless M, Weinberg U. Tumor treating fields: Concept, evidence and future. Expert Opin Drugs. 2011;20(8):1099-106.
Stupp R, Hegi ME, Idbaih A, et al. Tumor treating fields added to standard chemotherapy in newly diagnosed glioblastoma (GBM): fInal results of a randomized, multicenter, phase III trial. In: Program and abstracts of the 2017 Annual Meeting of the American Association for Cancer Research; April 1-5, 2017; Washington, DC. Abstract LBA AACR CT007.