Cancer cells divide and multiply rapidly within the metastases in the brain. These cancer cells carry different types of electrically charged elements that play a role during the cell division process. Other healthy cells in the brain multiply at a much slower rate, if at all.

TTFields Mechanism of Action

The NovoTTF-100M device used in this trial delivers very low intensity, alternating electric fields to the tumor site through the scalp. These fields are known as Tumor Treating Fields or TTFields. Preclinical studies showed that due to the shape and size of cancer cells when they are multiplying, TTFields cause electrically-charged cellular components of these cells to change their location within the dividing cell, disrupting their normal function and ultimately leading to cell death. In addition, cancer cells also contain miniature building blocks which act as tiny motors in moving essential parts of the cells from place to place. TTFields interfere with the normal orientation of these tiny motors since they are electrically-charged as well. As a result of these two effects, tumor cell division is slowed, results in cellular death or cell division reversal leading to inhibition of tumor growth after continuous exposure to TTFields. Preliminary data also indicate that the TTFields may affect the healthy brain cells much less than cancer cells since healthy brain cells multiply at a much slower rate, if at all.

A summary of TTFields’ mechanism of action is illustrated in the following animation:

TTFIELDS ARE NOT APPROVED FOR THE TREATEMENT OF BRAIN METASTASIS. THE SAFETY AND EFFICACY OF TTFIELDS FOR BRAIN METASTASIS HAS NOT BEEN ESTABLISHED.

Past clinical experience

A number of systems developed to deliver TTFields to different tumors have been tested to date. The main difference between the previously tested systems and the NovoTTF-100M is the frequency of TTFields provided by each system. The frequency is adjusted by the manufacturer of the systems in order to optimize the treatment for each treated cancer, based on data from laboratory experiments.

The Optune® System is approved by the FDA for the treatment of recurrent and newly diagnosed glioblastoma, a type of aggressive primary brain cancer. The same system has a CE Mark in Europe for the treatment of glioblastoma (for more information about the approved indications for use, please consult with your doctor or refer to the product information sheet).

Side effects

Based on the science behind TTFields and the clinical results to date, the NovoTTF-100M System is not expected to have systemic side effects in patients suffering from brain metastasis from non-small cell lung cancer. In previous studies performed with Optune®, the system tested in glioblastoma, a high percentage of patients have experienced local skin irritation beneath the transducer arrays, which was mild to moderate in severity in the vast majority of cases.

In a previous clinical trial for recurrent GBM, the following device related adverse events were reported:

Medical device site reaction - 18 of 116 patients (16%)
Headache - 4 of 116 patients (3%)
Malaise - 2 of 116 patients (2%)
Muscle twitching - 1 of 116 patients (1%)
Fall - 1 of 116 patients (1%)
Skin ulcer - 1 of 116 patients (1%)

In the aforementioned study for non-small cell lung cancer, there were no serious side effects related by the study doctors to TTFields. The only side effect which was related to the device was mild to moderate skin irritation under the transducer arrays placed on the skin.

The information provided in this website is partial, and you should consult with your treating physician concerning the complete safety profile of TTFields.

Please note that while the adverse event information from the recurrent and newly diagnosed glioblastoma and the lung cancer trials may be relevant to use of the device for brain metastasis from non-small cell lung cancer, it is not specific to this condition. The safety profile of the device for brain metastasis from non-small cell lung cancer may be different.