Glioblastoma: Impact of Tumor-Treating Field Therapy
Insights From: Maciej Mrugala, MD, PhD, MPH, University of Washington Medical Center; Suriya Jeyapalan, MD, MPH, Tufts Medical Center; Daniela Bota, MD, UC Irvine Medical Center
Suriya Jeyapalan, MD, MPH: When I became the medical director of Neuro-Oncology at Tufts Medical Center, I had the privilege of participating in the EF-14 Trial. I tell everybody I came in at the 9th inning and I was a closer for the trial at Tufts Medical Center. Tufts actually enrolled 17 patients in this trial. And when I was looking at this data, I was very impressed with it. I think it’s confusing; there are a lot of people who didn’t participate in the trial who haven’t used it commercially. But the company’s called NovoCure and the device is called Optune. It’s basically these adhesive pads—the adhesive pads are made by 3M—and they have embedded ceramic electrodes that are in this conductive gel. You wear it front/back, right/left, like in the original trial, and then you have it connected to a device. The device has the battery in it—it has a computer in it—and what it does is it generates an alternate electrical field that is then targeted. You use a computer program to see the tumor, and you can put measurements in on the axilla, the circumference of the head, and the front/back. You can plug those into the software and you can create a map for which they can direct the rays toward the tumor. Why is that important? Because 90% of the time, the tumor comes back. It comes back within 2 cm of the resection cavity.
If you are going to generate an electrical field, you want to generate it to the area of concern. And that’s what the device does. Why is that important? Because people say, “Well, how do electrical fields cure my cancer?” I think everybody’s been told in the past that electric fields might cause my cancer. I’ve told the company they’re like Galileo: everybody always knew the earth was flat. We just knew it, right? And poor Galileo almost was burnt by the Pope because it was hierarchy to say that, “No, actually the Earth is round and I can prove it to you.” So, I think what this company has done has shown to everybody that everybody’s always assumed that, “Oh my God, my cellphone’s probably giving me a brain cancer” or “I shouldn’t be living too close to a power line.” But they don’t realize that actually electricity can be harnessed to do things that you want it to do, that could be beneficial, just like radiation as well.
So, the GBMs are actually very, very rare because of that and because the cells in the brain just don’t want to grow. And so, this is the perfect opportunity to test out this thing because there’s nothing else that should be dividing in the brain. When you’re generating these electrical fields, you really have a great targeted therapy toward these growing brain cells, which should not be growing. And I think at the end of the day, they proved it. I’m very glad they did, because as an oncologist, when I first did my fellowship in 1999, the 2-year survival for these patients with brain tumors was dismal, far under 10%, probably under 5% for all comers. And we’re now so much better, and in 15 years of my career. I just hope that by the time I retire, we’ll get even better.
Maciej Mrugala, MD, PhD, MPH: Tumor-treating fields are new to neuro-oncology. This technology has not been around in the clinical setting for that long. However, we now have FDA approval for the use of tumor-treating fields, in the form of the Optune device, in both recurrent glioblastoma patients and newly diagnosed patients. The study that led to the approval of the device in recurrent disease was conducted several years ago. Almost 300 patients were included in this study, and the study was comparing this new technology, tumor-treating fields, to the standard of care in the recurring glioblastoma. So, basically, chemotherapy was compared to tumor-treating fields.
The results of the study indicated that there was no real significant difference between the 2 arms. So, patients who received tumor-treating fields didn’t do better than patients who were on chemotherapy. However, in terms of side effects, there were definitely less side effects in the tumor-treating fields group than in the chemotherapy group. On that premise, the FDA granted the approval of the device for recurrent disease. Once this happened, the study in newly diagnosed patients was already in the making. Again, the idea behind doing this study was that tumor-treating fields might be more powerful when they are combined with chemotherapy.
The analogy can be given here to use radiation therapy in combination with temozolomide that we know is beneficial. For patients who receive both treatments, radiation and temozolomide, as shown by Roger Stupp almost 11 years ago now, this combination of treatment is better. Preclinical data with tumor-treating fields also indicated that when tumor-treating fields—which are actually antimitotic, they disrupt the process of mitosis—are provided in combination with chemotherapy, they actually result in better outcomes. That’s how the study in newly diagnosed patients was designed. This was really based on the original platform using radiation with temozolomide, so this was the control arm. And the study arm, it was the addition of the tumor-treating fields into the standard of care, so radiation and temozolomide.
This study showed significant improvement in overall survival of almost 5 months in patients who received tumor-treating fields with temozolomide, as opposed to patients who were treated with standard-of-care therapy. The interim analysis of this study was published last year, and we are anticipating the discussion and disclosure of the full data set at the Society of Neuro-Oncology meeting in November of 2016. We hope that the data will indicate that what we had seen in the interim analysis holds true and that, indeed, the addition of the tumor-treating fields to the standard of care significantly improves survival in patients with newly diagnosed glioblastoma.
Daniela Bota, MD: So, when we think about the impact of Optune on overall survival, we have to look at dual categories of patients. First of all, for the newly diagnosed patients: if Optune is started after the completion of radiation and temozolomide—and it’s used in combination with temozolomide—it is continued to be used after the first, and even the second, progression until the 2-year interval is reached.
The data that we have from the EF-14 study show an increasing survival of 5 months. Some people ask, “How much is 5 months?” But I want to remind you that actually the approval of temozolomide, or Temodar, was based on an increase of survival of 2 months. So, we think that this is a major step forward. If we look at the recurrent patients with glioblastoma, the way in which this device was approved, it was in a study where it was compared to physician choice of chemotherapy. And the results showed that the use of the device is as good as using chemotherapy. People survived as long, but with less side effects due to the toxicities of chemotherapy, as the device has very minimal side effects, and none of them systemic.