Optune, a noninvasive device that delivers tumor-treating fields to the brain, provides oncologists, specifically those who treat glioblastoma multiforme, an opportunity to apply technology as part of their standard treatment regimen.
Eric Wong, MD
It’s not often that oncologists get to be the first to utilize cutting-edge technology.
“Traditionally, technology and devices are within the domain of neurosurgeons and radiation oncologists,” said Eric Wong, MD.
But Optune, a noninvasive device that delivers tumor-treating fields (TTFields) to the brain, provides oncologists, specifically those who treat glioblastoma multiforme (GBM), an opportunity to apply technology as part of their standard treatment regimen.
“This device has proven improved efficacy when compared to chemotherapy, it does not have serious adverse events like chemotherapy, and the patient’s quality of life is good,” said Wong, associate professor, neurology, Harvard Medical School, co-director, Brain Tumor Center, Beth Israel Deaconess Medical Center.
Wong will deliver a talk on the topic of TTFields and how the technology can be applied within GBM and beyond on November 10that the34th Annual Chemotherapy Foundation Symposium.
TTFields, administered by the Optune device, was first approved in 2011 as a monotherapy for adult patients with GBM that recurred or progressed after chemotherapy. That approval was based on a prospective, randomized, open label, active parallel control trial which compared
the effectiveness and safety outcomes of recurrent GBM subjects treated with Optune to those treated with an effective best standard of care chemotherapy. Wong was one of three physicians to present the data to the FDA.
In the study, the median survival was 6.6 in the Optune arm versus 6.0 months with standard chemotherapy (HR 0.86 [95% CI 0.66-1.12]; P=0.27) and the progression-free survival rate (PFS) at 6 months was 21.4% with Optune compared to 15.1% in the control arm (P=0.13). Responses were more common in the Optune arm with 14% of patients responding versus 9.6% in the control arm (P=0.19).1
In October 2015, the FDA approved Optune in combination with adjuvant temozolomide as a treatment for patients with newly diagnosed GBM following surgery, chemotherapy, and radiation therapy, based on an improvement in survival seen in the phase III EF-14 trial.
“In this phase III study in which patients received adjuvant temozolomide plus tumor treating field or adjuvant temozolomide alone, tumor treating field was clearly superior in terms of patients having a longer overall survival and also a longer progression-free survival,” said Wong.
The trial included 695 patients who were randomized in a 2:1 ratio to receive adjuvant therapy with Optune plus temozolomide or temozolomide alone. After a minimum follow-up of 18 months, the risk of progression or death was reduced by 37% with the addition of Optune to temozolomide. The median PFS was 7.1 months with the combination compared with 4.0 months with temozolomide alone (HR, 0.63; P = .001). The median OS was 19.4 months with Optune compared with 16.6 months with temozolomide alone.
In both trials, Optune proved to be well tolerated, said Wong.
Toxicities are primarily dermatological, and include scalp irritation and scalp burn. In more extreme cases, ulcerations or skin breakdown can occur, he said. Minor skin toxicities are typically treated with a topical high potency corticosteroid cream, while more severe toxicities may require temporary suspension of treatment.
Optune works by attaching directly to the patient’s head to deliver electromagnetic field therapy using low-intensity electrical fields to the brain. The device is portable and battery-operated. The FDA approved a smaller and lighter version of Optune in July 2016.
“It is basically an alternating electric field that is at a frequency of 200 kilohertz,” said Wong. “To give some perspective, this is within the borderline between radio waves and microwave range.”
This technique is thought to slow or reverse tumor growth by inhibiting mitosis during metaphase, anaphase and telophase, explained Wong.
There are additional trials looking at Optune within the neuro-oncology space, said Wong. The treatment is being investigated in combination with bevacizumab (Avastin) in recurrent GBM as well as with stereotactic radiosurgery.
A phase III randomized trial is also currently accruing patients, which will look at the efficacy of tumor treating fields in non-small cell lung (NSCLC) cancer brain metastasis, said Wong.
In addition, the treatment is being investigated outside of the brain cancer space. There are trials in pancreatic, ovarian, mesothelioma, and NSCLC looking at the Optune in combination with several different treatments.
It is exciting to see something that originated in brain cancer expand outside of it, said Wong.
“It is very interesting that traditionally most of the treatments against malignant gliomas come from outside of this disease site. For example, a drug is approved in breast cancer, lymphoma, lung cancer, and then gets adopted into clinical trials for glioblastoma,” said Wong. “This is happening in the reverse order and it is quite interesting and it really exciting to see a therapy that is showing efficacy in glioblastoma be applied outside of this disease site in other malignancies.”
Stupp, R., Wong E, Kanner A, et al “NovoTTF-100A versus physician’s choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment .modality.” Eur J Cancer 48(14): 2192-202