Round 1: Patient Factors and Treatment Decision-Making

The debate begins with a younger, high-functioning patient with favorable biology. The panelists explore how patient characteristics and preferences influence treatment planning, with discussion focused on feasibility, adherence, and the role of shared decision-making.

To see arguments related to managing suspected pseudoprogression, see Round 2.

To see arguments related to biomarker-guided decision-making, see Round 3.

Dr Minesh Mehta: Our first round is going to be about patient factors that influence treatment decision-making and so we will take cases where there are very special, unique, and pertinent patient-related factors that are critical and crucial. 

So the first case that we're going to be looking at here is a 46-year-old woman, so we're taking a very young person, who has a newly diagnosed IDH-wildtype glioblastoma. She undergoes a gross total resection. Now you've got a young patient, female, who's had a gross total resection, with a fantastic performance status, ECOG 0. The MGMT status is methylated, so again, giving more favorable prognostic variables for this patient and the patient has now completed concurrent radiation and temozolomide, has tolerated the therapy well, has had no major significant side effects from this. There is minimal residual neurologic deficit at completion of all of this. She's off steroids and now she has to transition to maintenance therapy. 

The social history is also relevant here. She's employed full time in a senior professional role, which she is continuing to work on. She lives alone. That's an important consideration that we'll hear about in a bit. And she's physically very, very active, and by the way, is a frequent traveler for her job. And that may also come into context as we discuss what we should do. So what is the appropriate maintenance strategy for this patient following chemo radiotherapy? 

Dr Rupesh Kotecha: But I think a key part of that first slide were the patient-specific factors here, and I think they make this decision very straightforward. This patient, as he mentioned, is young. She has an excellent performance status. She's had a gross total resection, and she is MGMT methylated. Those are all the most favorable features for a patient that we would see who has this type of diagnosis. 

To frame this, I'm going to go through some of the data from the pivotal EF-14 study, which was performed and really supports the use of TTFields in a patient such as this. This is the design of that EF-14 study. This was an open-label, randomized phase 3 trial of TTFields in newly diagnosed GBM. In this study, we had 695 patients who enrolled and randomized in a one-to-two ratio to temozolomide alone or temozolomide plus Tumor Treating Fields. The primary endpoint was progression-free survival, and the secondary endpoint was overall survival. 

The key thing is to note the baseline characteristics, and this will be important to frame our discussions and our topics as we're thinking about patients who would be candidates for TTFields. This study, patients were generally younger, and actually this case example of somebody who's even younger than this. The median KPS was 90. This patient has an ECOG of 0 that correlates very well. And again, a third of the patients were MGMT methylated. 

The key thing to note here is the outcomes. We have a statistically significant improvement in progression-free survival from 4 months to 6.7 months. And then the second part, this is something that we rarely see in the GBM space, a statistically significant and a clinically meaningful benefit in overall survival. So 16 months for patients treated with temozolomide alone, or 20.9 months for patients who are treated with temozolomide and TTFields. 

The second thing to note in this particular study is that overall survival, as we have patients who have longer-term follow-up. If you look at patients who have 2-, 3-, 4-, or even 5-year survival, you see those curves actually start to widen with time. That means that patients who have a long-term survival are going to even benefit more from TTFields therapy. 

Now, some of the key social factors that were mentioned, I think they were highlighted, but are definitely not detractors from the use of TTFields in this patient. She is a young professional, but TTFields are a portable ambulatory device. They weigh a couple of pounds. They can be put into a backpack. They can be put into a larger purse. The second part is that, yes, she is a woman, but she can cover the TTFields array on her head. One can use a scarf, she can use a hat, or there are patients who actually wear it openly. Finally, the aspect of travel is commonly brought up. Again, TTFields actually approved as an ambulatory device. We know that patients will move around and potentially travel with the device. The device itself is TSA compliant. You can take it on an airplane, and the power supply itself is internationally compatible. 

And then finally, before I turn it over to my debate opponent, one of the most powerful subgroup analyses that has come out of the EF-14 study is the importance of usage and long-term survival. In fact, actually, this patient, being young, having a good performance status, not having neurologic deficits, those are all features and factors that are associated with somebody who has a high expected usage. And again, if she does have that high usage, she would have the longest expected survival with this treatment. 

Dr Ashley Parham Ghiaseddin: And I think Dr Kotecha has made a lot of great points here that I think is going to be very difficult to try to convince you otherwise. I think that the main one that I would put out as one reason why a patient like this may not use Tumor Treating Fields in the newly diagnosed setting would be if there was an available clinical trial for that patient. So something in NCCN guidelines that we look at for glioblastoma in both newly diagnosed and recurrent setting is if there is a clinical trial available for that patient, then that is something we really want to recommend for those patients to go on and use. And unfortunately, many of our clinical trials are still behind on the data that we're looking at from EF-14, where they may not allow patients to use Tumor Treating Fields as part of their clinical trial. Now, I won't be debating that, but I think we can agree based off of the EF-14 data that Tumor Treating Fields does have a valid place in the treatment paradigm for patients who have glioblastoma. 

The other thing that I would look at is not necessarily why you wouldn't recommend Tumor Treating Fields to this specific patient, but maybe what are some reasons in your clinic that they may not consider using Tumor Treating Fields or have difficulty using Tumor Treating Fields and why they may consider that as an option maybe later on in their treatment pathway. Lifestyle burden is one reason that they may consider this could be a concern. You do have to wear the arrays on average over a 1-month period for at least 18 hours per day. Some of the challenges could include wearing the battery pack, which is about 2 to 3 pounds. So it's not heavy, but managing that equipment could be a barrier for that patient. 

They do need to sleep with the device on. That's a good way that they can bank hours. They may travel with this device, and regular head shaving is also needed because this is actually involving adhesive electrode arrays on a shaved scalp that are connected to wires, and patients typically are changing those arrays every 2 to 3 days. And if you think about the Florida summers, sometimes they may even do a 1-to-2 days changing. And for someone who's young, they're active, traveling frequency, this level of device dependence may feel restrictive. Cosmetic and social concerns as well, and there could be some social discomfort, unwanted attention that patients may have. When we think about younger patients, personal identity concerns could be an issue as well as the idea that the patient's treatment philosophy of wanting normalcy could really have the sensation of wanting to avoid feeling like a medicalized patient, that they're always thinking about their diagnosis, and having a device like this is a constant reminder of their illness. 

So I think a strategy that you can use in the clinic, because I'm giving you all reasons why maybe they would be apprehensive of using, is trying to have those patients think about this device as a way to control their disease, and that they have the power to use the device. The more you use it, as Dr Kotecha showed you on that last slide, the greater the benefit so that having more use will lead to a better response. And in a patient that's MGMT methylated, this would be a good reason for them to want to use it.