WCLC 2021 | What are tumor treating fields?

It’s a pleasure to talk to you today about tumor treating fields, which is a very novel form of anti-mitotic therapy. We are all very used to, and familiar, with anti-mitotic chemotherapeutic drugs, for example. But this is a non-drug type of a therapy. It’s a non-invasive therapy. It’s loco-regional in nature. And its predominant mode of action is to inhibit mitosis and therefore it’s an anti-mitotic treatment. It utilizes low intensity, medium frequency, alternating electrical fields, and these alternating electrical fields induce replication stress. This causes DNA damage in cancer cells, and because it’s anti-mitotic in nature, the DNA damage is not repaired and therefore cells then go on to die.

Typically, the TTFields therapy uses 200 kHz, it’s FDA approved in certain indications. Its first approval was in recurrent glioblastoma. But its significance was truly demonstrated in a Phase III randomized trial in newly diagnosed glioblastoma, where there was a significant long-term survival advantage and this then led to FDA approval in newly diagnosed glioblastoma. In several countries around the world, this has now become a standardly available routine therapy on top of the conventional chemotherapy and radiation that’s used for these patients.

It is recommended as an NCCN Category 1 adjuvant therapy for patients with newly diagnosed glioblastoma. More recently, it has received approval in malignant pleural mesothelioma. In multiple in-vitro and in-vivo trials, TTFields, especially in lung cancer models, have demonstrated anti-mitotic activity. There have even been Phase I and Phase II trials of non-small cell lung cancer where an initial hint of activity/efficacy has been established. When used with chemotherapy, and the frequency there is a little bit different, it’s used at 150 kHz, that’s where it’s used for first line unresectable malignant pleural mesothelioma.

So you change the frequency from 200 to 150 based on the specific histology of the tumor that you’re dealing with. Many histologies have common frequencies that can be used. Some histologies need a different frequency. So therefore mesothelioma is treated with 150 kHz. Brain metastases, in general, are treated with 200 kHz. So this is sort of the overall background of TTField therapy, a non-invasive loco-regional anti-mitotic alternating electrical field low intensity therapy that requires continuous utilization with the patients applying the current to the region of the body that is being targeted for therapy.