Hello. Good evening, everyone. Welcome to Chicago. Welcome to ASCO, and welcome to Novocure's post-PANOVA-3 investor event. It's my great pleasure to host the investment community. It's only Saturday at ASCO, but we've had just a tremendous meeting so far from a booth that was active, sort of every minute that was open, and of course to the presentation that we're going to review in this meeting again today of our phase III data in pancreatic cancer. My name's Bill Doyle. I'm the Executive Chairman of Novocure, and I want to start with just a very quick observation about where we are as a company. I had the great privilege of meeting Yoram Palti now over 25 years ago, at the Technion in Haifa, Israel. I was a you know, kind of a young, overconfident executive at Johnson & Johnson at the time.
And he pulled me aside with this idea. And I, in fact, I didn't know what the idea was going to be, but what he said was a, you know, a really different idea. And it turned out to be the idea to target the electrical properties of cancer cells rather than their chemical properties. It was on that observation, that idea, that we built the company Novocure, and for 25 years, we started with all the things that one must do to bring a cancer therapy to patients: preclinical work, clinical work. We're also literally a struggling startup, which means, you know, raising funding, convincing good people to come to work for us, to help us, convincing great investigators, to, work with us in the clinic, and convincing patients and their families to, try what certainly at the beginning was considered, a crazy idea.
But we're at a pivotal point now, because while we've built this foundation, treating patients with glioblastoma, we are now bringing this platform into a number of other incredibly difficult-to-treat cancers. We've launched now in non-small cell lung cancer after platinum failure, and we will be filing very soon our for regulatory approval to treat patients who have brain metastases from non-small cell lung cancer. And what we're going to talk about today, patients who have locally advanced pancreatic cancer. So this is the agenda. Ashley's going to talk a little bit more and give you some more detail about where we are as a company. And then the real meat of the presentation, our Chief Medical Officer, Nicolas Leupin, will talk about pancreatic cancer. And then Dr. Vincent Picozzi, the PI on the PANOVA-3 trial, will describe the data for you.
And then Ashley will wrap up and we'll have Q&A. So with that, I'm going to turn the clicker over to Ashley.
Thank you, Bill, and thank you to everyone as well in the room and to the many people that are joining us online. It really is an exciting day, and we're thrilled to be here with all of you. I just want you to recognize yourself, right? Our mission at Novocure is clear. We are focused on one thing. Together with our patients, we're striving to extend survival in some of the most aggressive forms of cancer, and we do that through the development and commercialization of Tumor Treating Fields. Those of you in the room know very well what Tumor Treating Fields are, but I think it's always important to just remind ourselves and anchor what is this that we're doing. Tumor Treating Fields use electric fields that exert physical forces to kill cancer cells via a variety of mechanisms. We know that there is an anti-mitotic effect.
We know that we can inhibit DNA damage repair, and we're increasingly learning about the induction of immune activation and immunogenic cell death, so we have a therapeutic platform that is perfectly suited to be used in combination with a variety of systemic agents as we look to target some of the most aggressive forms of cancer, and we're so excited to be here today adding yet another tumor type to that list with the positive phase III data in pancreatic cancer. Tumor Treating Fields are electric fields. We deliver them in a device, so you can see here on the side our commercial device on the left, my left, my right, your left, for Optune Gio and GBM, and on the other side for Optune Lua in non-small cell lung cancer. In all of our indications, we have an electric field generator that generates the field.
Those are connected to a set of transducer arrays, disposable arrays. This is a device that the patients incorporate into their daily living and carry around in an over-the-shoulder bag or a backpack. And you can see it integrates quite well into daily living. And I hope many of you guys have a chance to talk to someone with personal experience with that today. It is such an exciting time to be at Novocure. Bill alluded to this, but we are now standing on the shoulders of an incredibly strong business in GBM, where we have more than $600 million in net revenue, the best chance for extended long-term survival in newly diagnosed GBM, more than 4,000 active patients on therapy. That is our foundation, but we now have three additional solid tumors with high unmet need where Tumor Treating Fields has really moved the outcomes for patients.
I was reflecting with some of our other executives this morning that this is the third year in a row that we've been on podium at ASCO with positive data, which is really incredible, so in non-small cell lung cancer, you know that we extend overall survival in metastatic post-platinum failure. We've launched that in the U.S. in October and are now actively launching in Germany, really profound effect, particularly in combination with ICI. Our data last year in brain metastases also showed an extension in the time to intracranial progression, and importantly today, we're thrilled to share the survival results from the PANOVA-3 trial, so a therapeutic platform that really is touching on many of these tumors where other systemic therapies have not been able to make it advance.
So we're very proud of, proud of this and excited to share more about the specific data in pancreatic today. But I'm going to hand it over now to Dr. Nicolas Leupin, who is our Chief Medical Officer, who's going to give an overview of the pancreatic cancer space.
Thank you, Ashley.
It's a real pleasure to be here tonight with you. I'll try to frame a bit the pancreatic cancer indication in the coming minutes. So here we go. If I'm not mistaken, yes. So pancreatic cancer remains one of the most aggressive cancers in the world today. It's the third leading cause of cancer death in the U.S., the fourth in Europe. As we can see on that first slide, the incidence is increasing, especially in the developed countries. Reasons for that is an aging patient population and some lifestyle-related risk factors. Projections show that in 2030, it's probably going to be the second leading cause of cancer-related death. What is important is that today still we have a five-year survival of about 13%, one out of ten.
On the right panel, you see our three main regions, United States, Germany, and Japan, with the annual patients that are expected to be PANOVA-3 eligible. To just give you an idea of how many patients we're speaking about. Now, if we go into a bit more details and we look at the disease in itself, well, we have to see that despite numerous trials in the last 20 years, the majority of patients, as I was saying before, will die of this disease. One of the primary challenges physicians do face is the simple fact that patients in early stages just suffer from non-specific symptoms. Very, very difficult to differentiate from any other benign disease. And that leads to the observation that patients are diagnosed at later stages, which doesn't facilitate the fact.
And on top of that, you only have very limited options of treatment. While surgery is theoretically still the only curative option, only a small fraction of patients will be eligible for that. And following staging procedures, we actually differentiate between three stages. First of all, you have the resectable disease that is seen in less than 20% of the patients. There you can opt for surgery followed by adjuvant therapy. In some cases, you'll have borderline resectable disease where you'll try to give neoadjuvant chemotherapy just to try to reduce the tumor volume. And what we're speaking about tonight is the locally advanced pancreatic cancer that or the one that is not resectable. Now, on this slide, which is very important, we have on the right panel the resectable versus the unresectable stage. And what you can see is that we're speaking of vessels that are infiltrated.
Something we need to acknowledge is that for the surgeon, the pancreatic region, anatomical region, is one of the most challenging regions in the body, full of essential structures like celiac trunk and the mesenteric vein or artery. If those vessels are infiltrated or encased by the tumor by more than half, the situation is really unresectable. Now, coming to the treatment, we're facing that, as I was saying earlier, the options are really limited. Given more than 50% of the locally advanced cancer case, sorry, advanced pancreatic cancer patients only will receive a first-line treatment, and most of them will not survive the second line, the choice of the first line is extremely important. Now, only two regimens have actually been observed as being very effective. On one hand, the gemcitabine + nab-paclitaxel regimen, and then the FOLFIRINOX regimen.
The two are actually listed in the NCC N guidelines. They do have the category 2A recommendation, and they are used about 50/50. Now, what is important to know is that FOLFIRINOX comes with a lot of toxicities, way more than gemcitabine. And when we talk Gem's, FOLFIRINOX toxicities, these are neutropenia, neutropenias, febrile neutropenias, life-threatening neutropenias in some cases. We're also speaking of vomiting, nausea, and diarrhea. I'm not saying that Gem, nab-p aclitaxel doesn't come with toxicities, but they're way less important. Now, importantly is that a recent trial, led by the French showed that when compared to gemcitabine alone, FOLFIRINOX only showed a small benefit in PFS, but not in overall survival. So in that case, more chemotherapy actually doesn't turn out to be better. And that's also why we chose Gem, nab-p aclitaxel for our trial, because it is less toxic.
With TTFields, we were hoping that we could add some efficacy to a less toxic treatment. In summary, both treatments are actually effective, but I think it's important to keep in mind that FOLFIRINOX is more toxic. Now, coming to the end of that framing of pancreatic cancer, I'm really proud. I'm proud for two main reasons. First of all, because we had the courage to run such a trial in such a difficult-to-treat patient population, and because we can offer tonight a new option for those patients. Those data have been validated, largely validated by the simple fact that this abstract was accepted. It was shown just now at ASCO. It was also featured as Best of ASCO, and it was, as you know now, published in the JCO. These are three independent validations that show that those data are really important.
It's my big, big pleasure to introduce you to Dr. Picozzi, the principal investigator of the trial. Vince, may I ask you to join?
Thank you, Dr. Leupin. Well, that is me. Okay, and it's a pleasure to be with you this evening. And what I'd like to do is reprise the presentation I gave several hours ago to a medical audience, about the PANOVA-3 trial. Is this how we advance it?
Yeah.
Okay. Got it. Okay. So these were the key points of the presentation for the audience. PANOVA-3 is actually the very first, advanced phase trial in this particular stage of pancreatic cancer of patients who are locally advanced and unresectable to produce a positive outcome with respect to overall survival. And because these patients also are, in general, not curable because they're not operable, it leads to the second important point, in that quality of life is as important to the patients as quantity in many cases. This therapy also produced a positive benefit in terms of important quality of life parameters such as pain and overall health status. And this was accomplished, using, the device in a way that failed to produce significant systemic toxicity, skin toxicity, usually manageable, being the only major toxicity.
And so these conclusions led to the observation and the result that the PANOVA-3 results actually escalates Tumor Treating Fields and gemcitabine and nab-paclitaxel as a combination to a new standard of care for some patients with unresectable locally advanced pancreatic cancer. A conclusion actually that the discussant also agreed with as it turned out. So, very excited about that. Again, some more background. Pancreatic cancer overall has a survival of 13% at five years. When we're talking about adenocarcinoma, it's actually much less than that, only 8%. About a third of patients have the disease stage that we're talking about, locally advanced. This is probably the most complicated area of pancreatic cancer to treat. Progress has been very frustrating. Mostly, patients are treated with standard of care chemotherapy such as Dr. Leupin alluded to, either with radiation or without.
There haven't been a lot of trials in locally advanced pancreatic cancer. Those that have have been negative. In fact, the last big one was also one of mine, the LAPIS trial. To see success in the PANOVA-3 trial is particularly gratifying personally. This is the device for those that are unfamiliar. Certainly, there's a lot of open territory for progress in locally advanced pancreatic cancer. You're familiar with the concept of electrical fields altering cell division, inhibiting cancer growth as was described. You see a picture of how the device and the fields are used, through a battery pack and then paddles that are placed on a person's front and sides. You've heard that this approach has already been approved in other cancers in other countries.
There was an earlier clinical trial done by a physician named Rivera, which was done in 40 patients, two stages, 20 each, involving both patients with locally advanced and metastatic cancer of the pancreas and using gemcitabine either with or without nab-paclitaxel. And this, these experiences showed that the use of the device in this setting was feasible, safe, and actually brilliant results, very effective. That led to the creation of the PANOVA-3 trial, which takes the patients I've described, but is actually very liberal in terms of who it includes, including patients with what are called ECOG performance status two. These are patients that are out of bed or chair the majority of the day, but not normally functioning. Receiving the standard gemcitabine and nab-paclitaxel treatment were randomized either to receive use of the Tumor Treating Fields device or not.
This was a very large trial over five years, encompassing much of the COVID pandemic year, which had a definite impact on practice in general and trial eligibility and enrollment. It took place on a worldwide basis in about 200 centers in 20 countries. People were followed and treated in the traditional way, and then when they progressed, followed monthly for outcome. Here we see the major study endpoints that are being analyzed, the primary endpoint being overall survival. Secondary endpoints were a variety, including local survival, overall local progression-free survival. Excuse me, overall progression-free survival, some quality of life parameters, and other things that might help understand the use of the device, including importantly safety.
Something that was envisioned after the trial started and was added as a post hoc analysis was looking not just at local progression, but distant progression, meaning progression in the area of the pancreas, distant progression elsewhere throughout your body. And that ends up becoming a very important observation, as, as you'll see in a sec. So, here's the patient population. The total number of people enrolled was 571. This also may be the largest trial in locally advanced pancreas cancer ever done. I think it is, in a randomized fashion. That forms what we call the intent to treat population. Those patients that actually started therapy were evaluable for safety. And patients were then regrouped, based on whether they were able to complete a month of chemotherapy or a month of device use.
Those that were become what we know as the modified intent to treat population, a little over 400 patients. These are their characteristics. They're fairly standard for patients with locally advanced pancreatic cancer. However, I, I will call attention in particular to the 3 or 4% of people who were performance status two, and also the significant number of people, about 30%, that had CA 19-9 greater than 1,000, which actually indicates a probability of occult metastatic disease of over 90%. So many of these patients actually may have had metastatic disease that was unrecognized. Here's how the treatment was given. You can see that the treatment was equivalent in the two arms and for a duration that's fairly typical of people with pancreas cancer of this stage. Here you can see the TTFields device. People ended up wearing the device about 15 hours a day.
So it's quite a commitment to its use and really speaks to the devotion and enthusiasm of the patients for this. And that again was equivalent between the groups, as was the secondary therapies that were applied after a patient progressed. The analysis took place after patients had been analyzed and followed for a bit more than a year. And of course, the really exciting point was there was a clearly statistically significant difference between using the device or not. In quantitative terms, it was about two months, but with a hazard ratio of 0.82 and a p-value of 0.03, clearly statistically significant. That difference actually grew when the modified intent-to-treat population was looked at to about three months and more statistically significant. So a clear positive result with respect to quality of life.
But as I mentioned, well, before I get to that, let's take a look at some of the secondary endpoints. Here we looked at both progression-free survival and local progression-free survival. Although there was a statistically significant difference at one year, and although both progression-free survivals trended in favor of use of the device, they did not quite achieve statistical significance. Here's where the observations about distant progression-free survival become important. Obviously, the concept was the device would be directed at the primary tumor, but very interestingly and perhaps surprisingly, when visible detection of the cancer outside of the region of the pancreas, that's to say detection of metastatic disease was seen, there was again a statistically significant difference in favor of use of the device, which prompts a lot of interesting speculation as to why that might be.
I consider this difference particularly significant given the fact that probably, a meaningful number of the patients had metastatic disease all along, and it just wasn't recognized. This is going to be an important point for the use of the device going forward. As I mentioned, people in this situation are concerned not just with quantity of life, but quality of life. For some, it's even more important. I think, particularly rewarding was not just quantity of life was improved, but quality of life was improved. The quality of life parameter that people with pancreatic cancer struggle with the most is pain. It's a significant factor for about 85% of people. Here you see a very significant delay in progression of pain in patients of over six months. Again, very significant.
Believe me, this is the single most important thing to patients. The quality of life benefits extended beyond pain. There were some quality of life forms that were used that are standard in treating pancreatic cancer. Here we see a person, not just pain, but digestive symptoms, which are also key in pancreatic cancer, as well as some global health parameters such as function, psychosocial functioning, expectations for the future. We are also benefited by the use of the device. It really was not just something that improved the length of life, but the quality of life and the quality of the journey. Important to patients and their families. Using the device proved very safe. The toxicity detected was similar to the use of gemcitabine, nab-paclitaxel, and other published experiences.
And the two arms were similar to one another, except for the increase in skin toxicity that was seen with the use of the device. That was obviously to be expected to some extent. And if we look at that a bit more in detail, what we see is that skin toxicity really was the only meaningful extra toxicity that the device conveyed. Most of the toxicity was mild and easily treatable, but there were a small group of people, between 70% and 80%, that had such severe toxicity that it compromised use of the device. I, if I can editorialize for a sec, I actually think part of the reason for this is that oncologists are not dermatologists, and most have not progressed beyond what I used to call the seven rules of dermatology.
I think this is an area that can be improved with more sophisticated guidance for oncologists in terms of how to treat the dermatological conditions. In any event, I hope that you feel that the key takeaway points I shared with the audience, you've been convinced of, and that is that in fact this was a positive, in fact, the first positive trial in this disease state in terms of overall survival. The benefit extended beyond quantity of life and extended to quality of life in a way that was meaningful. Finally, toxicity was really limited to skin toxicity and manageable.
As such, as I stated, and actually has been already affirmed by the leaders of the pancreatic cancer programs, both at Dana-Farber Cancer Institute and Memorial Sloan Kettering Cancer Center, this established Tumor Treating Fields with gemcitabine, nab-paclitaxel as a potential, and I think not even potential. It is a, a new, a type of a new standard therapy for locally advanced pancreatic cancer. As was stated by Ashley and Nicolas, this was published today in the Journal of Clinical Oncology. Thank you.
All right. So we will go to questions soon, but we did want to take one moment to say, where do we go from here? Right? So thank you again, Dr. Vincent Picozzi for the presentation. He hinted at the discussions, questions, discussant questions, but I think we were also very pleased with the message that was on the podium from the discussant there, really reaffirming how transformative this is and the potential for a new standard of care. So we're heads down, focused on getting this to patients as soon as possible. This just takes you through the timeline of when the top line analysis came out, in December, so late Q4 of last year.
Nicolas and his teams, as well as the entire company, were busy over the course of the first two quarters preparing the clinical study report and the manuscript, and the presentation, which was live today, and now the team is focused on the regulatory submission. So we would expect that to go in in the back half of this year. We are very focused on those pre-submission discussions right now, and we'll get this in as soon as possible, and we would then expect to launch immediately after that regulatory approval, which, you know, time will tell how long that takes, but we would anchor you to about a nine-month assumption post-submission, which we will confirm through approval, again, pending the amount of interactive review that we have. But we fully expect and we're prepared for a commercial launch next year in this indication.
That's PANOVA-3, but we're not done in pancreatic cancer. So we also have a phase two single-arm trial, the PANOVA-4 trial that is studying Tumor Treating Fields in combination with the same gemcitabine, nab-paclitaxel protocol and atezolizumab, which is an IO in metastatic pancreatic cancer. So this tests two interesting questions that were not addressed in PANOVA-3. The first is, how applicable is this to the metastatic patient population? Dr. Vincent Picozzi alluded to the advanced stage of many of these patients, but we need, we need to test this in a metastatic population directly. And it also tests the potential synergy with the IO combination. We do know that Tumor Treating Fields induce immunogenic cell death, and we do know that IOs tend to be synergistic with products that induce immunogenic cell death.
So we're very excited based on what we've seen in our preclinical models and LUNAR and the phase two data that we'll see a similar effect here in pancreatic cancer. That data will be out in the first half of next year, and we'll then decide on the next steps on the other side of that. And we're also not done just in pancreatic cancer. So if we zoom back out and look at the mission of Novocure as a whole, while we have teams squarely focused on the regulatory submission for pancreatic, we also have a huge amount of focus on the successful launch in lung. We are rolling that out in the U.S. That was approved earlier this year in Germany as well. And then we are preparing for approval in Japan later this year, we hope.
We are also then focused on advancing the rest of the pipeline, which is both this submission to the FDA for PANOVA-3, the metastatic data to the FDA this year as well. The final enrollments in our TRIDENT and PANOVA-4 trial have concluded. We're in the data follow-up period for those two trials, which we'll read out early next year. On the product innovation side, one of the cool things about being a med tech company in a biotech space is that you get to develop not only the clinical pipeline, but also the product pipeline. We have several key innovations that were launched or are launching this year. The first is the MyNovocure Patient app, which is a whole new set of software engagements, ways to engage and support the patient journey.
We have rolled out our new array in all of our geographies, but we're finishing up to make sure that we touch every patient with that new array in all of these geographies. And then our product innovation teams are focused on taking some of those similar advances and bringing them to the torso array so that we can see a similar increase, hopefully, in patient comfort and usability in the torso. So we have an exciting future, and I think that's the one key message we want everybody to take away today.
We're very proud of this pancreatic cancer data, but we're also very proud and excited about the phase of the company where we are now with a solid foundation in GBM and really three product launches that are either already underway or anticipated before the end of next year with an opportunity to reach so many additional patients with aggressive forms of cancer. And with that, I'm going to open it back up to the room. And I know we have many questions that have come in online, so we're going to have help facilitating both the live and the virtual input here, but I'll open the floor to questions. Yes.
Hi. Hello. Jonathan Chang from Leerink Partners. Thanks for taking the questions. Maybe first question for Dr. Vincent Picozzi. How do you think about weighing the survival benefit achieved in this study versus the other considerations associated with wearing the device, including the commitment required from patients, as you suggested? And then the second question, a clarification question. Do patients undergo surgery post-treatment in the PANOVA-3 study? And if so, can you discuss the potential impact of this on the study results?
With respect to the first question, unfortunately, progress in pancreatic cancer comes in small increments. The two-month improvement overall survival, which was actually three months in the modified intent to treat population, is characteristic of the magnitude of improvement survival in positive trials in pancreatic cancer, such as the NAPOLI-3 trial, but is that something that's significant to the patients? It's absolutely significant to the patients and their families. And I would emphasize, here's where the improvement in quality of life is in some ways equally, if not more than important, as the quality of life. People are not just living longer, they're living better. And finally, I would say that I would think of these results as a foundation, a stepping stone to bigger things using the device, which opens up many avenues for additional treatment.
So this is just the beginning of an advance, I believe, in pancreatic cancer that the device makes possible. With respect to your second question, in this study, as I recall, the groups using the device and not both had surgical resection rates of about between 7% and 10%. That's actually characteristic of this population, and similar numbers are seen in other studies like the LAPACT study and the LAPIS study. It turns out that, although Nicolas showed you these nice stages, they're actually more of a biological continuum. And even when you're sure a person's operable, they sometimes are not. And even when you're sure they're not operable, sometimes they are. So I would say the results here are characteristic of that.
Hey there, Jessica Fye, J.P. Morgan. I have three questions. What is your hypothesis for why distant PFS hit? You mentioned that was sort of a little surprising. What are some reasons that we can read across from this trial to PANOVA-4, and what are some reasons for caution in jumping to the conclusion that PANOVA-4 would impress? And beyond surgery, what were the other subsequent therapies? I think they were balanced, but what were the other things that patients went on to?
I'm going to ask you to repeat those questions one at a time and a bit louder, please.
Yeah. What's your hypothesis for why distant PFS hit?
What's my hypothesis for why distant PFS was improved? Okay. I think there are several hypotheses, but I know the one that's the most intriguing is, that the device actually is inducing what's known in the literature as an abscopal effect, and that is, there's an immunological reaction to the cancer that the device is stimulating that's enabling it to fight cancer elsewhere. There are other hypotheses that could be advanced, but I think that's the one that may fit the best with the preclinical data that exists.
What are some reasons that we can read across from this trial to PANOVA-4, and what are some reasons for caution in kind of jumping to the conclusion that PANOVA-4 will impress?
So maybe I can take that question and thank you for asking it. So I think we need to differentiate both trials, right? One is locally advanced, the other is metastatic. Now, having said that, we have twice the same treatment plus then for PANOVA-4, a PD-1 inhibitor. And I think in the light of that intriguing observation of that distant PFS, where maybe we have, based on some preclinical data, some immunological background, I think I'm very optimistic towards the PANOVA-4 trial, as we call it, you know, in the light of the PD-1 inhibitor. And I'm I cannot wait until those data read out next year, to see what we get with the addition of a PD-1 inhibitor. But this is certainly one of the big topics of our discussions that we're having right now. Yes.
Maybe you want to.
Oh, I would agree completely, Nicolas. I think that, again, it's likely the PANOVA-3 trial contained a significant number of people with metastatic disease. And if we reflect on the fact that ultimately about 90% of people with pancreatic cancer will develop metastatic disease either sooner or later, that's one of the reasons I think for being optimistic about the future of the device, because it has a potential benefit for virtually every patient with pancreatic cancer if developed correctly.
Doctor, so I would add, you know, I always am apprehensive about these kinds of questions, right? Because we'll get the data and we'll see it in due course. But the other reason, or another reason, you know, if we looked at our LUNAR data, which is metastatic non-small cell lung cancer, where we saw the real benefit was in the combination of Tumor Treating Fields and IO in that setting. So it's not just preclinical and pancreatic, but we have a very real randomized data set in another difficult metastatic setting.
Thank you for making a very, very important point. I think we can start now with those three indications, GBM, lung, and pancreatic, to put the puzzle pieces a bit together and start to draw one conclusion to the other. So that might be all in all why we're very optimistic for those data.
The last one was just, what were the other subsequent therapies that patients went on to? I think you said 7%-10% had surgery, but what did other patients do?
Okay. Well, about half of patients received additional chemotherapy. That's actually a somewhat low number, compared to what would be expected, and probably it's reflective of two things. Number one, the fact that the study took place in so many different centers around the world with so many different treatment patterns, and it's also probably reflective of the fact that the study took place during the COVID era, which definitely influenced patients' attitudes when dealing with a terminal disease. About 15% got radiotherapy, and as I mentioned, between seven and 10% received surgery.
I would like to ask you that, number one, what is important in such a treatment is that what I said before is in those patients, that's why that first line choice is so critical. That's why you need to hit right the first time, because only 50% receive then a second line treatment. And then, in addition to the radiotherapy, what we saw was in most of the cases, first of all, it was absolutely balanced in two arms. And second, what they got was the usual chemotherapies, including oxaliplatin, leucovorin, irinotecan and 5-FU. So probably, some of them got FOLFIRINOX. And that shows that even after gemcitabine, paclitaxel plus TTFields, you can get the usual chemotherapies.
This is an online question that we received. Why do you believe that the PFS and ORR were not statistically significant? And how do you think that will impact the way physicians view this data?
I think that the issue with PFS and ORR is that our current mode of assessing it isn't very accurate. It turns out CT imaging only gives a crude sense of what the true dimensions of the cancer are, and also, we have to remember that the cancer is actually about 75% stroma and scar and only 25% cancer, so when pancreas cancer responds to treatment, it's not like a balloon that deflates. I think it was more like Swiss cheese with more holes in it, and it has the same dimensions, and so CT imaging is very good at showing getting worse. It's not very good at showing better, and so I think it's a, there's an underassessment of the true impact on, local disease. Now, do I think it will influence physician attitudes? That's a good question. I'm not 100% sure. It depends on who the physician is.
I think the really savvy physicians will know better, and they'll know, you know, what the limitations of assessing PFS are. I think the very, I'll say the more basic physicians will overlook the PFS and OS and won't even consider it, and they'll just look at the data on quality and quantity of life. It's the physicians in the middle that may have some trouble assembling that data, but we'll have to see. I'm not sure about that.
That's Jonathan Chang from Leerink again. Thanks for taking the follow-up. Can you provide some thoughts on the skin adverse events observed, and the degree that those events impacted wear and how long patients stayed with the device?
So, as you saw, over 90% of the patients really, once they started using the device, were able to use it effectively without significant toxicity. When the toxicities occurred, they generally occurred over a few weeks' time, and they generally took a few weeks to resolve. So that would be the approximate timeframe of what happened.
I think what is important is that we didn't see anything new to what we already knew, and the other thing is that gemcitabine and paclitaxel did not increase in any way the skin lesions, so what we're seeing is what we're also seeing in other trials.
You alluded to the opportunities that we have in product development. This won't happen overnight, but this is one of the things that we are actively working on in our next generation arrays, our different skin-facing materials that are very promising, in our laboratories. And we've made this point, you know, over time too, from a business perspective, as we make these improvements, we continue to innovate. That also provides patent protection that, you know, as long as we continue to innovate, helps us maintain our position as the not only the premier provider of Tumor Treating Fields, but the only provider of Tumor Treating Fields in our geographies.
And if I may just add to that, I mean, you know, the vast majority is absolutely reversible and only grade one and grade two. So again, nothing new.
Okay. We're going back to another online question. The trial showed pain, a pain-free survival benefit. Can you please speak to why that matters to this patient population? And then also, as a follow-up question to that, could any of that benefit have been attributed to painkillers? Were painkillers tracked in the study?
I apologize. I'm just having a tough time hearing the questions. Could you state the first one again and just a bit more loudly, and then we'll go on to the second?
Certainly. The trial showed a progression-free survival benefit. Can you share why that matters to this patient population?
Well, it means everything to them. This sort of takes us into the philosophy of life, but first of all, it's when your life is challenged that you realize how precious life is. And we in our society are so privileged with all the things that we can enjoy. Many, many people, most people actually, will do almost anything to survive. So that two-month difference, although it may not seem a lot, from an outsider's point of view to a patient and their families is tremendously significant, particularly if it means there's something special that they can do, like a Christmas holiday with their family or someone's wedding or the birth of a grandchild. Those things are so important to patients. I can't even tell you how important they are. So those are absolutely important differences. And people, of course, are always hoping for more.
My patients, after a bar is achieved, they're always raising the bar. So, there's no expectation that they're limited by that. So, that's absolutely critical to them and their families.
Dr. Picozzi, part of the question too was, and you've, I think, differentiated this very well. There's the duration and the quality. So specifically with respect to the pain-free, I mean, this is a tumor that can be painful. So maybe you could comment on the value of the pain-free observation.
Pain is the foremost complication in pancreatic cancer. It occurs in about 85%-90% of people. It's the thing that people are most afraid of. So, being able to mitigate that is huge. Again, the way I describe things when I'm dealing with a patient who has a terminal disease is I try to say to them, you know, I'm hoping to help you write the final chapter of the story of your life. I'm going to give you the pencil and the paper, but you've got to write it. Okay? So basically, I'm trying to make possible what they want to do with the rest of their life, understanding that it's limited, like all of us should feel our lives are limited. In my view, we should all see life through the eyes of cancer patients.
And so, being able to be free of pain and not limited by that is what makes that extra life possible for them to write their story.
Okay. This next question is in regards to treatment. How relevant is GnP in your practice? And why do you think more than half of the physicians still prefer FOLFIRINOX given its toxicity, tolerability issues, and the dosing?
First of all, I think I would challenge that more than half of physicians prefer FOLFIRINOX. I'm not sure that that's accurate from my perspective. Right now, there's a significant number of people that use gemcitabine-based therapy and a significant number of people that use thyr
oid-based therapy. When I give talks about this choice, I'll show a slide with a dozen different characteristics on it. It relates to your age. It relates to your driving. It relates to your comorbidities. It relates to side effects, your insurance, your genetic profile, all kinds of things. And so it's actually a good thing that there isn't just an answer. There are multiple answers. And I even think that this is almost too simplistic an answer, but Gem/Abraxane is still extremely relevant in people, in practice today.
Again, I don't see that the majority of people are using FOLFIRINOX-based treatments.
One point that maybe I'll make here, you know, as the Tumor Treating Field historian, on the stage, we have seen in every preclinical and clinical study that we've done that Tumor Treating Fields is either additive or synergistic with any pharmacology with which we've combined it and has never potentiated the toxicity. You know, we consistently see, you know, skin irritation under the arrays, and that's all we see. So while we've done this phase three trial, and you have to pick a therapy, and we made the decision to, you know, in consultation with our investigators, to start with Gem/Abraxane because, in large measure because of its toxicity profile compared to FOLFIRINOX, we understand FOLFIRINOX is used, and there's nothing that we know of that says Tumor Treating Fields cannot be used with FOLFIRINOX.
You know, we've talked about this as a first step in our program to treat pancreatic cancer. You should expect to hear more from us. We've talked about the combination with atezolizumab that's under trial now. You should expect to hear more from us about combinations with standard chemotherapies and other exciting therapies that are emerging.
I think the way I view these results, to my mind, as important as they are, is this is just a foundation. This is just a first step. And I would be forward-thinking in terms of what treatment for pancreatic cancer is going to look like three to five years from now, which is going to be, I can assure you, quite different from what we know today and quite possibly in a much more hopeful, promising, successful way. So I would be thinking about, in a field that's going to start changing rapidly, not how this is being deployed today, but how it's going to be deployed in the future.
Again, we've always said of Tumor Treating Fields as whatever the best pharmacology is available, we can make it better with our physical modality.
I was making a joke with Ashley on the way, and I told her to think of this like bacon, in that bacon can make anything better. And the same is true with Tumor Treating Fields. It has the potential to work with so many different agents, not just the ones we know, but many of the lines of research that are being developed, many of the class of new drugs being developed, and it has the potential to make many of those better. So, it is the sort of thing that you might see in almost any stage of pancreatic cancer with almost any systemic treatment. As I see the future.
Thank you. And a final question. Could you speak to the reception at ASCO to this data?
I'm sorry. Could you repeat that, please?
What was the reception at ASCO like to this data today?
I, from the number of text messages I got immediately after the presentation, I would say it was extremely successful. I think it was very well received. It's not common in pancreatic cancer where you have a clearly positive trial. So, I think you will see that this presentation, which is actually going to be reprised through the Best of ASCO mechanism all around the country and all around the world, is going to attract quite a lot of interest.
Echoed that. It was both in the room on podium where Dr. Picozzi did a wonderful job presenting, but it was also echoed in the discussion. So for those of you that were in the room there, heard him reiterate this as a standard therapy option that really offered, you know, an impressive and important survival benefit. But we're also hearing this at the booth, and we're just hearing it from our prescribing community generally. It's a lot of fun to be able to go and now really reap the benefits of being a multi-indication platform therapy because we're able to have the dots connected between a variety of solid tumors. And I think this feels like the year where that's really starting to come together. We feel it at our medical booth.
We feel it as we're talking to investigators, and we're really excited and focused on getting this data to the FDA so that we can then bring that message to our prescribers and bring this therapy to the patients who really need it.
Right. And that's what the Best of ASCO is. It's what ASCO thinks are the things that practitioners all around the world really need to know, the things that are going to be practice changing. So this is the whole society saying, we think you really need to know about this because it's going to be important to your practice.
All right.
All right. Thank you. To everyone in the room, but, of course, the many more people who are participating by the webcast, as always, we thank you for your interest in Novocure. We need to get back to work to get this into the FDA. Thank you all.