GL:    Good afternoon everyone. I am very happy to moderate this important session and round-table discussion on innovative treatments for solid tumours, in particular for glioblastoma and mesotheliomas, and a special focus on the use of tumour-treating fields as a novel modality for these diseases. I am a neuro-oncologist working in Padua, Italy, and I’m an expert in particular for glioblastoma patients and the new treatment modality in this setting of patients. So I’m very happy to introduce three important and nice speakers. I have the pleasure to introduce Professor Dean Fennell.

DF:    Thank you. Yes, I’m Dean Fennell, Professor of Thoracic Medical Oncology based in the UK in Leicester.

TUP:  My name is Tadeja Urbanic-Purkart. I’m a neurologist, neuro-oncologist, and I’m the Head of the Outpatient Clinic at the Medical University of Graz in Austria.

HB:   My name is Helen Bulbeck, I’m Director of Policy and Services at Brainstrust, the brain cancer people. We’re a patient advocacy organisation and support patients and caregivers on their journey.

GL:    So, as you know, glioblastoma and mesothelioma are two very difficult tumours, both in terms of treatment, because we have not had new efficacious treatment in the last years, and also for the patients and their caregivers because we have two diseases that are very difficult to improve the quality of life, also for the patients and for the caregiver. So it’s very important to have the possibility to offer to patients a new treatment. So I want to ask you what is the possibility, what is the new treatment available for these patients, in particular for mesothelioma disease and then for glioblastoma.

DF:    Mesothelioma, as you say, a lethal cancer, relatively rare cancer but one that has been increasing over the last thirty years globally. We had a standard of care that was defined in the early 2000s, actually 2003, and that was pemetrexed/cisplatin chemotherapy. It really wasn’t until 2021 that we had a change in practice so there has been very little advance in the frontline setting, actually. The TTFields, of course, represents one of those from the FDA licensing point of view. So the latest treatment we have, and it’s the treatment that pretty much everybody will get if they’re fit enough, is combination immunotherapy using ipilimumab and nivolumab. Those patients will then go on to receive chemotherapy typically in the second line. That was about 2021. We had, this year actually, data showing chemoimmunotherapy as a potentially superior… well, it was actually in the trial, a phase III pivotal study called IND.227 showing a significant improvement over chemotherapy alone with the addition of anti-PD1 pembrolizumab. So at the moment that would be the latest advance but in terms of licence space we’re really talking about ipilimumab and nivolumab.

GL:    And about glioblastoma?

TUP:  So for glioblastoma we have our standard of care since 2005, nothing really changed since the Stupp regimen which is radiochemotherapy with temozolomide, which is an alkylating agent. We all are aware that this agent is working very well for those who are methylated but not for those who are unmethylated. Since then TTFields added to this very small armamentarium in the primary therapy of glioblastoma, but this is a very valuable addition since in this phase III trial, EF-14, we are all very well aware that there has been shown an addition of about five months to the overall survival with the addition of this medical device. So this is the standard of care throughout the world but only in the NCCN guidelines have TTFields got into the primary therapy as a fixed point. In Europe and many other countries, the TTFields reimbursement and the mode with which you can prescribe it are actually different. There is a diversity of prescriptional options and possibilities.

GL:    So do you use TTFields as a standard treatment in your hospital for glioblastoma patients?

TUP:  Yes, we can do this.

GL:    So in the last year about glioblastoma patients the tumour-treating fields represents maybe the only improvement in association to the Stupp treatment in this very aggressive disease. So sometimes patients ask us information about quality of life, the impact of the tumour-treating fields on quality of life. So I want to ask you how important is quality of life in the context of a patient with a tumour?

HB:   The other thing that I just want to say too is that there is an equity of access issue to TTFields because in the UK it’s not available on the NHS. But in terms of quality of life, my experience working with patients and caregivers on this pathway is that increasingly they’re trying to step outside the Stupp protocol because they know it’s not delivering the outcomes they want. But, at the end of the day, it comes down to the individual’s context and their appetite for risk and what their values are. So I have patients who opt to have no treatment and don’t want to spend the time exploring for potentially what is the Holy Grail, but then I’ve got others that maybe have got a significant life event that they’re waiting for, like the birth of a child, and they’ll try absolutely anything. I think one of the benefits, is that you can use it alongside other treatments.

GL:    Yes, this point is very important because in this aggressive disease quality of life has to be the measured endpoint in the treatment of these patients. So we have for glioblastoma patients a study demonstrating that TTF does not impact on quality of life. So the patients can be treated with this device in a good manner. I want to ask, in mesothelioma patients have we data on quality of life and the results?

DF:    We don’t have randomised trial data for that reason, given that patients would receive chemotherapy which, of course, has its own burden of toxicity, what that increment in toxicity alterations in quality of life over and above the standard of care is. Nevertheless, from the study that was published, the expectation in terms of adverse events is that it was very similar to what we would expect with standard of care. We have good experience in managing the standard toxicities of chemotherapy. So, yes, the overall burden of additional toxicity is minimal, if any at all, from what we know so far.

GL:    What do you think about quality of life in your patients treated with TTFields?

TUP:  I can just give a very brief answer to this. They are all, just as in this publication, they do not really have major issues. One of the major points that the patients report is that they are really happy that they have an indirect possibility to just do something for their own disease. This is when they are taking chemotherapy it’s just chemotherapy, it’s everywhere and you cannot really moderate where should this go. With TTFields you know that if you are good, if you just have a very good compliance, then you can help yourself a bit more. This is an active involvement so they tailor their way of disease. This is, for me, the most important part; the toxicity is just a skin one and this is manageable in most parts.

GL:    So we can offer this new treatment to our patients. But, in your opinion, what patients are the patients dedicated to be treated with this novel treatment?

DF:    As I mentioned, back in 2003 chemotherapy was the standard of care and the STELLAR trial was an incremental improvement over and above that, or at least that’s the result of that trial. Now, because we’ve had a change in the way in which we treat patients systemically, chemotherapy has been pushed actually to the second line for now while we give immunotherapy as our first-line treatment and chemotherapy as the second. But the rules will still be the same in terms of selection. We’d be looking for fit patients with an ECOG performance status of 0-1 with really any histological subtype of mesothelioma. As I say, the toxicity that we see from the addition of the TTFields from the STELLAR trial was really minimal, if anything, over and above historical expectations.

GL:    We have the same for glioblastoma patients – what is your experience? How do you decide?

TUP:  Probably for our indication it’s very important to have a very good social network or a very good caregiver. Because in mesothelioma probably I could put this on myself, but for glioblastoma this is not possible. So it’s very, very important to have a caregiver who does it, who is dedicated, who is just willing to learn and adapt.

GL:    Yes, an important point is that we have the possibility to use the same treatment for different tumours. So it’s not a frequent condition for pharmacological treatments. So this is a good opportunity to learn, better learn, how to use and which patients we can select to be patients. Of course, in glioblastoma patients we have the possibility to use TTFields as a standard treatment for newly diagnosed glioblastoma patients, but also after the first or second relapse in your context?

TUP:  No, the reimbursement in Austria says that patients with newly diagnosed glioblastoma are eligible for this therapy but it’s just like a standard EF-14 protocol. When they are finished their radiochemotherapy, you can give it as an adjunct to the adjuvant temozolomide.

GL:    Another aspect is the possibility to use TTFields also in case of toxicity for pharma, for drug treatments. What is your experience? Have you patients with these characteristics?

TUP:  Yes, I had one patient who just didn’t want to take chemotherapy after she experienced grade 4 hematologic toxicity with temozolomide. She was then on monotherapy with TTFields for almost ten months which was, of course, incredible in an unmethylated glioblastoma patient. This was a really good one single example, of course, because this is not per protocol, of course, but it’s allowed. So you can do this, it’s not off-label, it was still in the setting of primary diagnosis, the primary tumour, with the first treatment-related toxicity.

GL:    Another important aspect is that also all patients can be treated without problem with TTFields. At ESMO this year we have some abstracts analysing more than 4,000 patients, older patients, receiving TTFields and without particular difference between the general population. Moving on to the conclusion, the last consideration in why, for you, is it important to offer innovative treatment for these patients with mesothelioma?

DF:    It’s exceptionally important because it’s still a cancer of unmet need. We have very few treatments and where treatments exist we see clear benefit in terms of longer outcomes, survival outcomes, better quality of life. So when we run out of treatments there’s an inevitable cliff edge that is coming towards us. So, yes, one of the goals is really to maximise the number of treatments. This looks like something that really has efficacy and delivering that in the UK practice setting would be an addition to the armamentarium that we have to deal with this cancer.

GL:    Final consideration for glioblastoma patients and the possibility to offer this important treatment? What is the most important change in your practice?

TUP:  When we are counselling our patients we should be honest and what we shouldn’t do, what I observe, is project things that we think that are right for them or not right for them. The good thing is just to counsel them, to just present all the opportunities and let them choose and be active in their treatment process. So this is probably the best way to treat the patient and this also helps you to maintain a very high adherence.

GL:    So we have the possibility to use this new treatment without impact on the toxicity. How important is it for a patient with this aggressive disease and the possibility to use this treatment and also in combination with other active pharmacological treatment?

HB:   I just want to support what you said, it’s about that shared decision making. For somebody who is diagnosed with a life-limiting disease where they’ve only got maybe weeks or months, to have that conversation with them about what’s important to you, how do you want to remember this time, what are your goals? For them to have a treatment that can enable them to achieve those goals that’s not going to bring high toxicity levels, it’s absolutely key because that way they can continue to live their best possible day.

GL:    So an important point is the efficacy of this new treatment for patients with mesothelioma and glioblastoma. We know that we have two aggressive diseases and so the possibility to prolong the survival is an important endpoint with a good quality of life for these patients. So what is in your disease the clinical data we have from the literature and can we translate into your clinical practice?

DF:    Yes. The long-standing overall survival data for patients with chemotherapy alone was 12.1 months survival. It was hypothesised in the STELLAR trial that this would be increased, of course, with the addition of TTFields. The overall survival is over 20 months actually and that was despite having about a third of patients with the most aggressive forms of mesothelioma in that.

GL:    And for glioblastoma patients we have important data about that?

TUP:  Yes, we have data that in the primary setting in the EF-14 study the addition of tumour-treating fields to standard treatment after standard radiochemotherapy will prolong survival by about five months. So the Stupp trial was 16 months versus 20.9 months in this TTFields trial. What is probably very important is that at five years if you just see the data of all these glioblastoma patients all over the world, but this is mainly from American studies, the survival is about 7%, so 0-7%. Again, with the addition of tumour-treating fields, you have about three times as many patients alive at five years than without this treatment.

GL:    Great results and great opportunity. And as a patient association have you experience with longer survival with TTFields? What is your experience?

HB:   Because it comes with no toxicity apart from the skin irritation for some people, patients like it because it means that they can get on with their lives and achieve the goals that they’ve set. Also you’re not being driven by lots of hospital appointments all the time because you can self-manage. I think that gives a sense of control back to patients when in the early stages of diagnosis they feel they’ve lost all control. So having that network of people around them where they can manage it and live their lives the way they want to for an extended period of time is really important.

GL:    So we are coming to a conclusion and we talked about two important and aggressive diseases. At this time we can offer in addition to the standard treatment also this new modality, the tumour-treating fields. So it’s an important point for prolonged survival also without impacting quality of life. So I thank you for your co-moderation and thanks all of you for your attention.