Tumor-Treating Fields Continues to Garner Interest in Glioblastoma

Wenyin Shi, MD, PhD

Concurrent use of tumor-treating fields, radiation therapy, and temozolomide is under study as a potential treatment for patients with newly diagnosed, stage IV glioblastoma (GBM), explained Wenyin Shi, MD, PhD, in an interview with OncLive^® in advance of the 10th Annual Brain Tumor Symposium.

“At the upcoming brain tumor symposium, we’re going to discuss clinical trial developments at Jefferson, focusing on GBM. The main topic we’re going to discuss is an investigator-initiated trial conducted by our group, which is investigating combining tumor-treating fields with radiation treatment for patients with newly diagnosed GBM,” said Shi, professor and co-director of the Brain Tumor Center at Sidney Kimmel Cancer Center, and co-director of the Stereotactic Radiosurgery Program at Jefferson University Hospitals of Jefferson Health. We’re also going to discuss a trial in development, looking at thermal radiation treatment [with] brachytherapy for recurrent GBM.”

In the interview, Shi discussed new techniques in radiation and tumor-treating fields in glioblastoma and updates on clinical trials at Jefferson ahead of the annual meeting .

OncLive^®: What is the basis for evaluating tumor-treating fields plus radiation therapy in patients with newly diagnosed GBM?

Shi: GBM is the most threatening brain cancer in adults, with a very poor overall survival [OS]. Advances in GBM management have been slow, failing to meet the need for patients and their families. Most recently, a phase 3 randomized trial introduced a new treatment device, tumor-treating fields into the management of GBM. Based on the EF-14 trial [NCT00916409], patients who used tumor-treating fields had an improvement in OS of close to 5 months. The treatment is currently used when patients finish radiation treatment and concurrent temozolomide.

However, a lot of preclinical evidence suggests tumor-treating fields and radiation treatment have synergistic effects, so our group has initiated a trial to evaluate the feasibility and preliminary efficacy of combining tumor-treating fields with radiation treatment for patients with newly diagnosed GBM. We will enroll adult patients with newly diagnosed GBM who have a performance status over 60.

What have preliminary results shown?

The trial we have conducted and finished one trial that is combining tumor-treating fields with concurrent radiation treatment, and has enrolled 30 patients. Our preliminary data indicate that the progression-free survival is 9.3 months, which is significantly higher than historical controls, which vary from 5.2 months to 7.1 months.

Another trial done by an Israelian group of researchers provided the feasibility and tolerability evidence to support this concurrent regimen. Currently, this novel approach of combining tumor-treating fields with radiation treatment is being tested in a phase 3 randomized trial run by Novocure, which is the TRIDENT trial. The phase 3, randomized trial involving 950 patients is an international trial that is expected to open in over 150 sites globally. The trial is currently activated in the United States, Israel, and the southern European countries. The experimental regimen is exactly what we developed in the initial study using concurrent chemoradiation with tumor-treating fields.

Turning to the second trial, how could thermotherapy work synergistically with local brachytherapy?

GBM has a pattern of local recurrence. Over 90% of tumors will recur at the primary sites, so local therapy always has been a focus of GBM treatment. Previous studies have looked at accelerating radiation treatment dose. Unfortunately, that has not led to an improvement [in outcomes]. Some studies done by University of California, San Francisco demonstrated that if we use thermotherapy with local brachyradiation treatment, it can improve the OS of patients with GBM.

With this new technology, we utilize a very novel, nanoparticle that can produce thermotherapy and combine a device that’s constructed and developed by our group using high-dose radiation treatment to the resection cavity while giving thermotherapy concurrently for patients with recurrent disease. The study is currently in the preclinical phase; we are doing animal studies, and we’re looking to open the phase 2 study soon.

What are you looking forward to seeing at the symposium?

This is a very exciting time for the management of GBM, and, most recently, the World Health Organization [WHO] classification for GBM has gone through an iteration. We are entering into an advanced molecular area. Since the prior WHO classification, we were already using molecular guidance on diagnosis and treatment of GBM patients, but now it’s really in prime time, and significantly changes our diagnosis and management regimen. I’m excited to discuss new developments and [hear from] keynote speakers on new developments and different strategies of managing patients with