Educated Patient® Webinar: Biomarkers, Why Genomic Testing Matters

Ryan McDonald: Hello everyone, and welcome to today's live broadcast, Cure's Educated Patient Webinar, Biomarkers, Why Genomic Testing Matters. I'm Ryan McDonald, Associate Editorial Director for Cure Magazine, as presented by Cure, sponsored by Lilly Oncology, and in partnership with Cancer Support Community and ALK Positive. There are just a few important announcements before we begin. We encourage you to ask questions during the event, which you can submit by typing them in the Q&A box. Also you will be receiving a survey via email tomorrow. As a thank you for watching the full webinar and completing the survey, you will be entered to win one of three Visa gift cards. And now I would like to introduce you to those who will be leading today's discussion. We are pleased to be joined by today, by our moderator, Dr. Edward Kim, who is the Physician in Chief at City of Hope Orange County, and Vice Physician in Chief at City of Hope National Medical Center. Joining Dr. Kim will be Dr. Todd Bauer, a medical oncologist at Tennessee Oncology and a senior investigator at Sarah Cannon Research Institute. Dr. Eric Nadler, who is the medical director of US Oncology Health Informatics and Internet Oncology, Claire Sexton, who is - Saxton, who is the Vice President of Education and Outreach at Cancer Support Community, and Gina Hollenbeck, who is the President of ALK Positive. Thank you all for joining us today and I will now pass things off to Dr. Kim to begin the discussion.

Ed Kim: Thank you, Ryan, and I want to welcome everyone. We're really excited to be part of this panel today and really walk through a discussion about biomarkers and genomic testing, and clearly this has been a really important area that science has moved forward in. It's become essential, not only in oncology but in other areas as well. But certainly front and center in oncology and how we've been going through, and so to be able to moderate a discussion among these experts across the spectrum, as you can see, will have many different viewpoints on this, and so I will just get right started. Precision medicine, and especially cancer, what is it? How does personalized care differ from a traditional standard of care therapy? I'm going to start first with one of our docs. Todd, you want to take us out of the gates first, talk about that?

Todd Bauer: Yes, sure, thanks, I'd be glad to do that. First, welcome everybody tonight, I really appreciate the chance to be on and chat with you. Personalized medicine is the idea that we are picking out the best treatment we can for each and every individual patient. If you think about it, we treat cancer simply by where it starts, and if you line up 100 patients with lung cancer and give 100 patients with lung cancer the same drugs, you're going to get 100 different responses. [00:03:00] When I see a patient with a unique cancer or less common cancer, they always say "Do you ever see this?" Maybe I don't see a lot of it, but every single patient that I see, whether it's breast, lung or colon cancer, they are the only ones who has ever had or will ever had their exact cancer. And so the idea of personalized medicine is how do we best understand that cancer so that we can drill down, understand the weaknesses of that cancer, and give the best possible drug with the best chance to treat the cancer and with the lowest chance of toxicity to that patient? That's the idea of personalized medicine in my mind.

Ed Kim: Gina, from your perspective as someone who has been a strong advocate as well as in the healthcare field, what are your thoughts around this? Gina, did you hear me? Uh-oh, did I -

Gina Hollenbeck: As far as biomarker testing, I think that just like Dr. Bauer said, it's an opportunity for patients, and I think every patient should have the opportunity to look at the DNA of their particular cancer, find out what's driving it so that we can figure out how to stop it. I think of biomarker testing and targeted therapy as opportunities for patients.

Ed Kim: And Claire, from your perspective, what has this really meant? When we go away from standard of care, some people might be a little hesitant to hear that, that we're using something maybe futuristic or research-related.

Claire Saxton: And it certainly is something new for a lot of cancer patients and their loved ones to think about treating cancer not based on you have lung cancer or breast cancer, but based on what is the molecular makeup of your cancer, and what would best work as a treatment for that cancer? And so I think a lot of people find a lot of hope in personalized medicine in that they are getting the treatment that is best for them, and also a lot of these treatments are the most - the newest, the most innovative, and have shown to work well in these very specific subtypes of cancer, because a lot of patients, when they think about how do you treat your cancer, they're thinking about how is that whole type of cancer treated, like how is lung cancer treated, not how is lung cancer that has these specific test results, how is that best treated?

Ed Kim: No, I -

Todd Bauer: And -

Ed Kim: Certainly echo that. Go ahead.

Todd Bauer: I was just going to say, if patients or if folks are worried about it being too futuristic, I'd suggest [00:06:00] if we look in the rearview mirror, our history isn't so great with treating cancer. If we had all the answers, we wouldn't need to be running all these clinical trials to find newer and better drugs. And I have discussions with my patients all the time about the best drugs in the world to treat cancer right now I think are - most of them are still in clinical trials. We have some really good drugs out there, but drugs that were designed 15, 20 years ago, kind of traditional chemotherapy, think about the TV you were watching 15 or 20 years ago, or the car you were driving 15 or 20 years ago. Newer is better in the terms of science and what we understand about it. I love futuristic, I love cutting edge, it's so good for patients.

Ed Kim: Eric, from your standpoint, is this practical now? Is there a cost, an access aspect? This is right up your alley with the research that you do.

Eric Nadler: Thanks, Ed. Certainly practical, I think the challenges unfortunately are somewhat age-dependent. These drugs are very, very expensive in terms of their acquisitional cost, most being charged roughly 12 to $16,000 a month for these drugs, and I do think they offer excellent benefits, so that's a different question I think you'll ask later, Ed. But in regards to how do you get these? For most people under the age of 65, traditional insurance plans, there are ways, and the companies have been very generous at kind of brokering the ability of getting these drugs, even though they're of great cost under the age of 65. Over the age of 65, it can sometimes be a little more difficult, and granted, I'll let other people speak to this as well, of how easily obtainable these are and how much cost is borne by those people over the age of 65 who just have Part D of Medicare. But they offer tremendous, tremendous value, far more value when you do proper cost-effectiveness analyses than cytotoxic or traditional poisonous chemos, and it's just an exciting time, as everybody alluded to. These are really the forefront of what we're thinking about when we think about non-small cell lung cancer right now.

Ed Kim: I have to share a personal story. When I was two jobs ago, when I was at MD Anderson, and in the mid-2000s, in our department of thoracic oncology, we were conceiving an idea of a clinical trial in which we wanted to repeat biopsy patients after they had already been diagnosed, after they had been treated with chemotherapy, which then stopped working, we wanted to repeat a biopsy, use that - one of those core biopsies to assess [00:09:00] at the time, this was 2006, about 14 biomarkers that were very speculative, and try to see if we could match up a corresponding oral therapy with what the biomarkers showed. And this was the BATTLE trial, this - we had a lot of press about that, and we thought it was the right thing for patients because we wanted to push forward personalization. And I will tell you, at the time, we got some resistance from folks because we were told it was unethical to rebiopsy a person once they were diagnosed. And it just kind of shows you contextually where we've come in time in less than ten years from that. We published that study in 2011 and it's unbelievable now that we have so many ways that we want to assess markers and get biopsies, whether liquid, tissue, so there's a little context there for what we've all sort of lived through during this period.

Todd Bauer: And Ed -

Eric Nadler: It's amazing you mentioned - I'm sorry, Todd. It's amazing you mentioned, Ed, that the first commercially available, at Anderson, you were doing a little bit earlier, and Sloan and Farber, but the first commercially available to physicians or patients genetic test of any of these types of personalization or biomarkers is only 15 years old, it's 2006. And so we're only 15 years into this. It's amazing how far we've come. And now we have drugs for almost all of those 13 targets.

Todd Bauer: And what is driving that is the clinical development of these drugs, if - I started at Tennessee Oncology and Sarah Cannon about nine years ago, and I think we might have done 35 or 40 biopsies that entire first year, per clinical trial protocol. I bet we do 70 to 80 biopsies a month on our patients now because as we're developing these targeted drugs, it's a big ask of patients and I don't love doing biopsies that don't necessarily impact any individual patient's care, but in the setting of a clinical trial, if I'm developing a drug that I say works because it hits target X, the FDA is saying "Show me target X is there before you give the drug, give the drug, do another biopsy, and show that target X has been destroyed." And that is what is really driving all this, so there's a bigger ask of more biopsies, but it's science-driven and its data-driven and it's efficacy-driven. You think about it, some of the most recent drugs to come out, whether it have been larotrectinib or lorlatinib or selpercatinib, those drugs are approved on very small patient populations. We aren't developing drugs anymore to treat tens of thousands of patients. We're developing drugs to treat 1% of the patients [00:12:00] with this disease, and so you've got to show how that works. And in their - in due fairness to the FDA, they've gotten much better about saying "We get it, we can't expect 5,000 patients on a randomized trial to approve this drug," and so that's where we're seeing a lot of these targeted therapies come through, which are so much better for patients in terms of efficacy and side effect profile. If you think about it, I describe to patients all the time as if you can picture those old videos from - probably from World War II or Vietnam of carpet bombing, with the big B52s just flying over, just dropping out huge numbers of bombs, that's chemo. And you think back to the first Gulf War when we all stayed up watching those grainy black and green videos of the laser-guided missiles going down the bad guys' chimneys, that's targeted therapy. You get the bad guys and leave the good guys alone and you get them with more efficacy than if you're just carpet-bombing.

Ed Kim: No, and Claire, from your standpoint, as more and more healthcare providers are asking for biopsies and for repeats, what is your counsel to that?

Claire Saxton: I think that most patients, when they hear that they're being asked for a biopsy because they're being asked to see what treatment would work best for them, most patients see that as a helpful thing and as something that they really want to do. There are some barriers that still stand in some patients' way in terms of even just getting those biomarker tests paid for, but especially if you're talking about you want to do a second round of biomarker tests, and it's not part of the clinical trial where many of those costs would be covered, it can really depend on a case by case basis or an insurance by insurance basis whether the - those would be covered. But those are some things that at the Cancer Support Community, our Cancer Policy Institute works with other cancer nonprofits such as Longevity and ACS CAN on working both on the state level for the state issues that can cause problems with having those tests covered as well as on a national level. But I think once patients understand that there are - they're expensive tests, but there are tests out there that really can help you zero in on what is the best treatment for me, that really sounds like something that they want to be part of. [00:15:00]

Ed Kim: And Gina, as we transition to how we present that to patients, how we educate them and spread that word, I still remember when ROS1 was coming out and there was some disputes of that's too rare, we shouldn't test it, it's 1%. How - what should you tell - what's the message you give patients?

Gina Hollenbeck: In our support groups, we see people who have ALK-driven cancers. Sometime - they're not all lung cancers, predominantly they are because thankfully, lung cancer is leading the way and doing biomarker testing, but we have people who have breast cancer, skin cancer, sarcomas, brain cancers, all driven by ALK, and they're benefiting from the targeted therapies, and so that's the cool thing, to see that they're actually working or they're actually getting biomarker testing. But I think that when we talk to patients, I think it's so important that we ask about biomarker testing because it gives us a little bit more information about that person's particular cancer. We're really looking at that DNA. I feel like the more we know about the cancer, the more likely we are to defeat it and have longer life expectancies. I think Dr. Bauer brought up a really great point about just the very best stuff is right now in clinical trials, and a lot of people don't completely recognize that when it comes to clinical trials. I think that a lot of people think that you're a guinea pig or a lab rat, but in fact, it's just the opposite, and it's really where the very, very best and newest and most promising care is for people because we're just hitting the nail on the head, we're just getting there as far as really making this a chronic disease. We're not there yet, but we're getting there.

Todd Bauer: Ed, one way that I would think about that is if we look at all these individual durations, they're rare. ALK is three to 5%, ROS, one to 3%, FRAK, less than 1%, maybe.1%. But if you add up all of those, especially in lung cancer, you're talking 45 to 50% of the patients are going to have an actionable mutation or your treatment choice is going to be driven actionably. The FDA has approved two drugs in a - or three drugs, maybe, in a tissue agnostic way, pembrolizumab for MSI-high tumors and larotrectinib for TRK altered were the first two. It doesn't matter anymore where the cancer started, if you do the testing [INAUDIBLE] Sorry, guys, I'm not sure if that's me or not, I apologize. But if you test everyone, [00:18:00] you're likely to find alteration in some of your patients.

Claire Saxton: And just for - because I know that patients and caregivers and people who are newly diagnosed can get very confused by all of the alphabet soup that each of these mutations are named, but what really matters is getting the test and finding out where you test positive, whether that's the NTRK or MSI-high, you only have to remember the things that actually make a difference in how you would be treated, and so your oncologist can know about all the different mutations that are out there that could impact your treatment. But what matters is what do you test positive for, what shows as unique for your cancer that has a treatment associated with it that we know works fairly well for people with those mutations.

Eric Nadler: Could I -

Gina Hollenbeck: I think I -

Eric Nadler: Make one -

Gina Hollenbeck: Yes, sorry.

Eric Nadler: I'm sorry, go ahead. Go ahead, Gina.

Gina Hollenbeck: I was just going to say, as a patient, I just think it's so important that everybody gets tested because there's so many new things coming down the pipeline, and I - one great example of that is KRAS, there's been new targeted therapies for that. But all of the people who didn't get tested, who only got tested for ALK, ROS1 or EGFR, were kind of left out of that because they didn't know what was actually driving their cancer. I just think there's new things coming down the pipeline all the time, so it's so important that everybody knows exactly what's driving their personal cancer. Sorry, Eric.

Eric Nadler: Ed, I did have one quick comment, Ed, before we jump on. I think there's one smidge of caution, though, I just want to raise to the group that's assembled today. It looks like we have 65, 66 people. There are a number of - I think you can kind of loosely divide the information that comes from this testing into three categories: those in which we know what the right clinical answer is in regards to treatment, those in which we're hopeful that we may be able to develop things in the future, or may, but there is a third, and that is there's a lot of information and mutations and information that comes through in these reports that are probably not going to be actionable now, in the near future, and in the potentially distant future. There's a lot of noise in these too, and I think it's important to do your own research, to the patients, and also talk frankly with your oncologist, and they'll be frank with you, whether or not they think the information you're getting actually will lead to a therapy that we have right now or in trial and development right now, those which may be actionable in - [00:21:00] near future. And those, there are plenty that probably will never have clinical relevance, and that's important too. But getting the information is paramount and critical, and kind of having that discussion, that one molecular discussion with your oncologist about what this means and what it could mean in the future.

Ed Kim: That's well-stated, Eric. And what should we tell patients? I always try to tell them these days you need to take charge, because sometimes there can be so much information coming left and right. But what do we really need to tell them especially about biomarker testing and what they need to have in hand as they move forward? What do you think about that, Claire?

Claire Saxton: Well, certainly biomarker testing isn't actionable in quite a few circumstances. And so the first question is am I eligible for comprehensive biomarker testing? Are there biomarkers that I should be tested for? Those are big questions to be asking your oncology team, because different types of cancer are much more likely to have specific mutations that have drugs that are associated with doing well in terms of treatment. And lung cancer I think has the most actionable mutations, and in fact the Cancer Support Community has a biomarker tool for people with lung cancer where they can go to cancersupportcommunity.org/biomarkertool. And there they can answer a serious of about five questions and get information about what biomarkers should you be asking your oncology team about. And if you go to cancer-specific organizations, they can help you understand what biomarkers are appropriate in your cancer type. Or if there really aren't any biomarkers that can help your oncology team make a decision about what your cancer - what cancer treatment is right for you, there are other national resources like the patient guides from NCCN. Those are great in talking about what biomarkers you should be tested for, because the other thing that if you are going to a local [00:24:00] oncology team that maybe doesn't specialize and you have more of a rare cancer, we still need to do some education with physicians out there and with oncology healthcare professionals out there in terms of making sure that when it could help, that biomarker testing happens. And so it can always be good just to ask your oncology team, "Are there biomarkers I should be tested for?" And if you're having a hard time understanding, then also try to talk to and look at information from a cancer advocacy organization that can help you get that information in patient-friendly terms. Because like I say, the alphabet soup can really be overwhelming to patients.

Todd Bauer: So Claire, I'll submit it can be overwhelming to patients and it can be overwhelming to providers as well. Think about some of the oncologists out there. And full - I'm a community oncologist. I take care of all sorts of cancer. I do not specialize in any one thing. And there's a lot of information out there. I don't think there are any oncologists who don't want to best understand the best treatment for the patient in front of them. And there's always that dance of, "Well, I don't want to offend the doctor. I don't want to ask." Doctors should be asked. But I think one thing that we haven't addressed yet is not just what are we testing for, but who should be tested. So I've seen a couple of the questions come up and I've tried to answer a few of them in real-time on the chat box on the bottom. "I had this cancer, this cancer, and should I get testing now?" So who's the right patient to be tested? I think the right answer from my standpoint - I'd love to hear Dr. Kim's thoughts on this because I know he - and Dr. Nadler's as well. He thinks about them a lot. If a patient has metastatic cancer, they should have broad-based molecular profiling at least one time. If someone has a surgically-resected, treated with adjuvant chemotherapy, potentially-cured cancer, that may not be the right time for that test that runs $5,000 to $6,000 to do the testing, because it's not going to impact their treatment at that time. So if it's my mom I'm sitting in the room having the conversation with, and she had a cancer two years ago, she went through surgery, went through chemo and it's all gone, does she need to have testing now? Well, no. Let's pray that it's done and gone and we don't need any more information about it. And when the cancer - if a cancer were to recur, that would be the most real-time view of that particular cancer. Then it is metastatic. Then you do start to open up that world into clinical trials [00:27:00] and more rare indications for drugs like pembrolizumab has in MSI-high, or the TRK inhibitors do. So I think it's not just - and I'm a huge fan of profiling when appropriate. So metastatic cancer, yes. Curative intent, resected, done with chemo, probably not necessary right now. Though in some lung cancers that's probably evolving, as I'm sure Dr. Kim could comment on.

Ed Kim: Yes. Thanks, Todd. Certainly what my general practice is and what we try to espouse is anyone who shows up - and lung cancer's been a poster child as of late with the number of different markers that have been approved in drugs. But really at diagnosis, I consider genomic testing, these biomarkers as part of the initial staging and evaluation. So you have to have that information in hand. Once you've set [INAUDIBLE] therapy, then if the disease for instance, the drug stops working or the disease comes back or if it should pop up somewhere else, I like to do another evaluation at that point, because we now - we see that things can change. There can be resistance markers, or even there can be changes. Sometimes we use a liquid biopsy. I'm still a traditionalist and like to do tissue, because we have seen in even some percentages that are not insignificant ten to 15% where you can see transformation to a different type of cancer. So that's what I like. And just as you said, in early-stage lung cancer where patients are surgically resectable, there is now a new standard of care in lung cancer where we do not the whole comprehensive testing, but we do have a mutation, EGFR that we do test for in patients based on a recent phase 3 study. So it is exactly what we hope for, is that when patients have an advanced cancer that we want to test and find the best drug, but now moving each of these principles to the earlier stages so we can try and cure the patient and keep it away, that's really the key. So Gina, your thoughts on this?

Gina Hollenbeck: I think when it comes to biomarker testing, patients need to know basically three things. They need to know about opportunity, the time, and the cost. And so the first one is opportunity. They really just need to know that biomarker testing gives us more information about their cancer, but it doesn't necessarily tell us that we're going to find the perfect drug for them. So they just need to know that it's an opportunity to look for a targeted therapy. The second one is the time. When I was diagnosed in 2015, it took about two weeks to get a comprehensive next-gen sequencing back for me. I was pretty sick at that point, and every night [00:30:00] I went to bed, my husband was wondering if I was going to wake up. And so I think there's a sense of urgency for patients. As soon as they find out that they have lung cancer, they want somebody to do something about it the next day. And so sometimes waiting to actually find out what's driving the cancer and the best treatment is the best thing. So I think they need to be informed that there's a wait. And the last thing is the cost. And I insisted that I got next-gen sequencing, comprehensive biomarker testing each time I progressed, and I progressed five different times during this cancer journey since 2015. So on the first time that I actually was diagnosed, my insurance denied it, and they said that comprehensive biomarker testing was experimental and that targeted therapies - I think that's so funny. But that was back in 2015, so I got stuck with a $6,000 bill. But the cool thing is that almost every single one of the testing companies has a patient copay assistance program. They have some type of way that they can help patients pay for it. And usually the maximum amount that a patient will actually be expected to pay is about $100. And so that's something that I think that a lot of providers are a little bit sometimes leery about. If a patient - if their insurance doesn't pay for comprehensive biomarker testing, they're a little bit worried to stick the patient with that bill. But if you go and investigate a little bit more, all of the companies have some type of payment assistance programs.

Todd Bauer: It's funny you mention that. David Spiegel and I were having a discussion about this probably six years ago, right as some of these larger vendors were coming online. And we would sit down and spend 15 or 20 minutes having a discussion with a patient about, "Should we order it? What do we do with it? What if you get that bill for $6,000?" And if my kid comes home with like a $20 lunch room fee, I'm like "what did you spend this on?" So that's a lot of money. But yet we're ordering CT scans and PET scans left and right and never having a discussion won with it. So it just becomes a comfort level, and I think that molecular profiling at this time, certainly now, has turned into a standard-of-care procedure. There was a meeting. I want to say it was three years ago at the American Society of Clinical Oncology annual meeting. And it was sort of a debate session. And Skip Burris was on one side of molecule profiling, and there was another person on the other side. And the opening line was, "Well, CMS or the Center for Medicaid and Medicare Services just approved molecular profiling in this setting for metastatic cancer, so the debate has moved." So yes, it is paid for by insurance. And I still tell patients, "If you end up seeing an EOB from your insurance company saying 'Dr. Bauer's a terrible doctor, he wants to do this unlicensed test, it's completely unreasonable, he's going to cost [00:33:00] you $6,000.'" I'm like, "It's not unreasonable. It's not going to cost you $6,000 and I'm really doing my best for you." So it's how you frame that discussion. And I think the negative tests are also helpful in this. It's great when I see a test back that has EML4 ALK or ROS or RET or TRK mutations or fusions. But a negative test also keeps me from trying patients on drugs that were never destined to work for them anyway. So anything you get back on that testing is valuable information.

Ed Kim: Eric, your thoughts on this? How can we get more testing for folks and make sure they're educated on that?

Eric Nadler: I think my testing pattern mirrors yours. And I test almost everybody. I do lung cancer and sarcoma, so everybody's tested up front. And lung cancer and sarcoma is one of those cancers, it's not terribly helpful all the time. So I'm kind of dealing with either of those. Usually in terms of testing, that part, there are lots of mechanisms for getting that part tested. As I alluded to earlier there are a little bit of challenges occasionally getting the act [AUDIO SKIPS] somebody astutely mentioned in the question-and-answer, "Is this a kind of - is this unfair that there's that difference over whether or not a person's over the age of 65 or not?" And the answer to that question very shortly is based on the fact that it's Medicare itself, it's considered a form of kickback since the ability to augment these plans that the companies have are somewhat different over the age of 65 and under. But most of the time, I think I can speak for all five of us. Most of the time we're able to get testing done, not unburden a person with a bill, and most of the time you can get the drug in almost anybody's hand without crippling cost. And I think that's been my experience of 18 years now in clinical oncology, is there's almost always a way of getting it done. And whether I can't speak to Gina's organization, but whether or not they offer grants or things like that. So there's almost always a way to partner amongst a variety of team members and get both the testing and the appropriate drug in the patients who require and need it. That's been my experience. I can't - I won't speak for the rest of you, but -

Ed Kim: I think that wait time as Gina, as you talked about it, that two weeks in 2015, we haven't seen that move very much since -

Eric Nadler: [CROSSTALK], yes, unfortunately. [CROSSTALK] actually expanded it. It's not a joke. It was quicker when it was just sending the big three and what have you, and it was [INAUDIBLE] looking for ALK and [00:36:00] occasionally PCR. Next-generation sequencing's at least 14, 13 to 16 days I would say now.

Todd Bauer: Yes, but I think that there's value in that. And this is an important discussion that I think is - it's so important. Do I want to start a drug today because I can, just because I can start something and I'm going to feel better [AUDIO SKIPS] going to feel better? Or do I want to wait two weeks and find a drug that doesn't have a 35 or 40% chance of responding, but a 75 or 80% chance of responding with significantly less toxicity? So is it starting a drug to start it, or is it waiting a couple weeks to see if there is a better drug to start with better results for the patients? And we do see - so the easy thing in lung cancer right now, the no-brainer start-tomorrow is a chemotherapy/immunotherapy combination. That's easy. It's got a good chance for everybody. But the problem is there's data suggests that giving one of these targeted therapies, what we refer to as a tyrosine kinase inhibitor, is how the drug works, blocking signals. If you give that after you give immunotherapy, maybe you increase the risk of some of the side effects of that drug within the lung tissue itself. So in that case it becomes a safety issue. Yes, the easy route is easy, but it might actually not be the right drug and it might actually put patients at risk of side effects from that right drug when they try it. So I think this is that conversation as I describe with my patients. It's a slow, deep breath. We need to start this, but we need to make sure we're starting the right thing for you, not just starting something as we move forward. And I think if you have - I like to think, doesn't work at home all the time, that my words have some gravitas and influence. But my 12-year-old definitely say no. But being able to have that conversation, say, "Look, slow, deep breath. Two weeks is not going to change the outcome in this. But starting the wrong drug versus the right drug can have very big impacts." That's how we have to think about these things in the recurrent or metastatic setting. Not necessarily in adjuvant, but in the recurrent/metastatic setting.

Ed Kim: And I do think to that point, we have to figure out at what point do we have enough information to help treat a patient so we can get a test done earlier and quicker, versus how long do we wait? Just to Eric's point, is it now increasing because we're testing more markers and there's more therapies out there? I think one of the things we always want to try to do is contextualize these biomarkers, and make sure people understand they are just as important as the result of that CAT scan, of that biopsy, all of that, that it's all the same. You would not start therapy unless you had the results of a [00:39:00] certain scan back or others, and everybody's waiting for those radiology reports. But I get it. Many times patients are - first they show up to their primary care physician's office with a cough or something, and then it can be a couple months later and then an X-ray. And then a month after that, it's seeing an oncologist. And so now you might be three, four months into it by the time you're getting a biopsy, and now you got to wait two more weeks. It's like getting mashed potatoes at Thanksgiving and waiting for the turkey for another two hours because we didn't plan it correctly to cook it. It's just - it's one of those things. But I think we have to emphasize how important these markers are to make an informed decision these days in cancer. No, so anything, any solutions you all have to try and get it to less than two weeks, that would be great. But I really think that's got to be our next technology jump, is not to add 100 more markers but to try and get it quicker when we can get that for patients. So all right. What's the one thing, one advice you would give a patient? Let's say it's someone from out-of-state. They've contacted you, said they're going to go see their oncologist next week. And you're just going to give them information, a checklist. What is that one piece of information you're really going to tell them that when they go to that office, there's going to be a million things going through their mind? What is that advice you're going to give? So we'll just go around the table here. Gina, you first.

Gina Hollenbeck: My first thing is I always ask, "Have you had comprehensive biomarker testing?" I think that's really important. So make sure that just because they know that they have some type of cancer. But do we know everything about this cancer? So that's number one. And then number two is find a support group, somebody who is like you who's experienced the same thing that you can bounce your treatment off of. And that's been one of the things that's really been a game-changer for me, joining a Facebook support group where I could really learn. I was being treated by a community doctor who had one other ALK-positive patient. But when we joined that support group of 2,500 people from all over the world who are being treated in major medical institutions, we can see that the care is a little bit different. And so it's really important to be able to find somebody else who's experiencing the same thing and having some success in it.

Ed Kim: No, that's great. Claire?

Claire Saxton: Sure. And I would just add to what Gina said in terms of make sure you get from your oncologist exactly what type of cancer you have. And it's often more than just lung cancer. It could be small cell lung cancer or non-small cell lung cancer, so that you know exactly the type of cancer that you have. Ask[00:42:00] about if comprehensive biomarker testing is right for you. And if so, have you had it? And if so, what are the results? And what would those results mean for your treatment? And even for your prognosis, because in different cancers the biomarkers can also tell you - give you some kind of a sense of how aggressive that your cancer would be. And so, those are all good things to start off with just so that you have a good understanding of exactly what type of cancer are we dealing with here. And then I couldn't agree more with Gina's suggestion of joining a support group. If you're comfortable with online support groups, there are a number of them. Find one that really - that works for you and that has other people who have the same kind of cancer, if not even the same with the - Gina's organization where they all have the same biomarker results. Or if you prefer a more local support group, one that meets at your local hospital. Cancer Support Community and our Gilda's Clubs across the country have support groups that are local. Whatever works for you, because cancer treatment is a long haul. And talking to others who've been there can help you better understand what you're facing and give you tips for coping.

Ed Kim: Thanks. Eric?

Eric Nadler: I just wanted to mention to the group that it's a little bit of an oversimplification to say that there's usually one right best answer for the first thing when one embarks on a cancer journey to be offered to them. Sometimes there's two or different ways of skinning a cat, if you will. But in general, there's usually a good first thing to do. And without doing biomarker testing, you don't know what that is. Now there's plenty of diseases and still plenty of non-small cell lung cancer that the right answer is using traditional cytotoxic poisons to begin the journey or immunotherapy or both of those to begin the journey. But what I think we've really all reified amongst ourselves today is until you have all the information, you can't choose that first thing. So I don't want everybody who listens to this to think that molecular targets are necessarily the appropriate first step for everybody, or that they're even going to see a molecular target in their entire cancer continuum. There are plenty of cancers you don't. But I think it's important to get all of the information at the beginning [00:45:00] of the journey so you can make the best choices as you go through it. And I think that would be the most important thing to do, is get all your ducks in a row if you will or get all the information at the beginning.

Ed Kim: Todd?

Todd Bauer: I think there's so many super-important questions. I think question number one is do you feel comfortable with the person sitting across the room from you? So much of this cancer journey is that the relationship between the patient and the provider, and making sure that the decisions are made in conjunction, that that feels like a good relationship. I would love to say that I mix up Lorbrena better than anybody else in the world, but I don't. It's the same drug. I'm not a surgeon where technique is super important. My technique is in how I talk with patients. I think that that's so important to be able to connect with patients and do that. So all - Gina, Claire, Eric, all your points are super important and they're right from a factual-based standpoint. But it's got to feel right. And if you're going to pin me to the wall and say "what's the one main question you have to know," I think it really needs to be, "What is the most important thing that I haven't asked today that you need to tell me?" And patients ask me that all the time, and often they've asked all the questions and I'm out of answers and I do the best that I can. But it's to be able to say, "Are you being completely open and honest? Share with me the details," because that's the important part of the relationship I think between oncologist and patient, is that trust and that faith and that compassion that goes back-and-forth. And that's where I think the magic is between a doctor/physician or doctor/patient relationship.

Ed Kim: Yes, no, that's great. And I echo what you all said. I love the idea of really out of the gates finding an advocacy group. I can say that that hasn't necessarily been my verbiage, but I like learning as well. And so I think that really should be incorporated, especially now that everyone's more comfortable with online meeting people these days, especially over the last year-and-a-half or so. So I think that's great advice from that standpoint and just is the theme of today. We've been talking about why genomic testing matters, why biomarkers are important. I don't think people should be scared of that. I think we're all information-seekers, and especially when it's something that's affecting you, gosh, I would get as much information as you can. You have that right as a patient, as a caregiver who's acting on behalf of the patient to not only ask for it, but demand it. And I think you have to be your own advocate these days. And [00:48:00] it doesn't matter if you're going to a tertiary academic medical center or you're in the community. I've worked in both those scenarios. It's so important, and geography and access should not be an excuse to not get something that's really important as far as information. So I think that's a theme that we've all been reiterating there. There have been a lot of questions coming through. I think many of you have seen those come through the audience. I know we've tried to answer some of those. But what's one where - if you find one marker, do you expect to find another one or are they mutually exclusive? Eric, what are your thoughts on that?

Eric Nadler: Depends on the marker. There are a number of patients where you send them off and they come back with five or six markers, and unfortunately most of them are nonsense when that happens. For the typical kind of cancers where we think there is a so-called - in medical parlance we call it "driver mutation." ALK, EGFR, those being the most common that we [INAUDIBLE] about. Usually we think of them as being relatively mutually exclusive. That's not entirely true. Occasionally on case-reportable basis find a dual mutation in that setting. The other thing we haven't been mentioning, but I'll throw it out given this, is PD-L1 is tested routinely now, which is looking for potentially the validity of immunotherapy. So you're going to be seeing those on your reports, everybody. And sometimes those are paradoxically elevated and not being of great importance. Other times they're elevated truthfully, and they're of exceptional importance in how you determine it. So the answer is occasionally you will find more than one thing, and unfortunately they're sometimes confusing. And I'll be honest, and we've all kind of mentioned this before. Sometimes the person who's the clinician who you're seeing may or may not know with that specific combination what to think about. If you're - for example, MET. It's one of the unusual new mutations. That and ALK and EGFR can all be very, very high for PD-L1, except the PD-L1 isn't really telling the story there. And you kind of have to have been doing this for a while to know the nuances of that. So it's possible. I think that's a very convoluted way of answering that question, but it is very confusing.

Ed Kim: Yes, and I think it is just as you say. If I paraphrase correctly, it's a rare event. And so it's not the most common thing we see, but it can happen. We do prioritize certain markers ahead of others. So just as you mentioned, if you have a PD-L1, which is an immunotherapy sort of marker that's elevated, but you have [00:51:00] the presence of one of these other mutations, the mutations take precedence. So there is a rank order. They're not all created equal, and so - and Todd had talked about that earlier, about how you give sequencing on certain therapies. And there can be lack of effectiveness and even more toxicities. So I think these are all important aspects from that regard. One of the questions that came in was about a pathologist. Can they come in and discuss? Well with all due respect to pathologists, we don't want them discussing with patients. They're great people. They're excellent, but they're sometimes not the most patient-facing folks that we would say. I'm kidding. But -

Eric Nadler: In Norta, they always have all the clinical information. They've almost never seen the studies themselves often, and in the curve related to these drugs. So I think these discussions are best left in the hands of oncologists, I believe. I think everybody -

Ed Kim: They do very important work. We need them. We rely on them. But they are experts in their own area, and that's - but it is true that a lot of the biomarkers and the testing does intersect through them because they do handle the tissue, and that's a point where many places have reflex testing that's done. Other places don't, and so that can all add to the time situation that can occur. So it's a good question from one of our folks. We won't get into necessarily products or anything specific like that, but that there are multiple commercial tests out there that would sort of fit the definition of comprehensive genomic testing. There are some in-house that certain institutions have. And frankly, I think anything more than 50 to 100 genes is when you start getting into comprehensive testing category. I would not want somebody to get a five or ten-gene panel that those are left over from the early days. That I think is whatwe want to avoid. But I think what's really important especially to this audience is - and this has come up a few times in the questions - is that fear. It's scary to be diagnosed. And we really want to try and educate, push this information out there, make sure everyone feels informed on that. And so as we start getting to the top of the hour, I want to go around to each of you and let you sort of give your sort of final thoughts. One to two minutes on the summation of what we've talked about today, what we've talked about the best advice. What is - what do you want to articulate most to our audience who have been great about asking about these questions? And one that came in, Claire, about the liquid biopsy, you can include that too in your explanation, so you can do that. So [00:54:00] let's go reverse order this time. Eric, why don't you start us off?

Eric Nadler: So I apologize. I've been looking at some of the questions just to see if I could tie some of them into a minute. And I think I can. I alluded to it earlier, but the challenge is the world has gotten a lot more personalized. These biomarkers are much more important and prevalent than they've ever been before. You're talking to a somewhat potentially lung-centric panel here. And if you told me 20 years ago lung would be the cancer we know the most about the molecular underpinnings of it, I would've thought you were crazy. I think everybody would agree. But I want to caution everybody because there are a lot of people - there are people here with MDS in this room tonight and there are people here with breast cancer in this room tonight and all different types of sarcomas. And unfortunately we're not quite prostate cancer. We're not quite as far along in those other cancers. Now, that does not mean this testing isn't important, these discussions aren't important. And if there is any research protocols in your area that pertain to your disease, I would strongly encourage going on clinicaltrials.gov or other different ways of looking at that. But I would say that unfortunately, the advances that we see so strongly in lung cancer haven't completely dissipated to the remainder of oncology to the same degree. That doesn't mean it won't over the next few years or decade or so. But it hasn't yet, and I think this is continued work we need to do. So I don't want to discourage anybody who does not have a particular cancer or not that you shouldn't consider trials or other types of innovation. It exists in every field of oncology, with every disease, more exciting now than ever. But a lot of what we talked about was very tightly relegated around these few processes and these few diseases. And I'm not trying to discourage anybody, but that is important to mention and note.

Ed Kim: Claire?

Claire Saxton: Sure. That's a great point, Eric. I think that that's part of the questions that you should be asking your oncology team. "Is comprehensive biomarker testing right for me? Am I eligible for it?" Because it tends to be mostly used in metastatic and advanced disease. But even in that scenario, not every type of cancer has something that's actionable. So that's a great question for your healthcare team. One thing that Dr. Kim brought up earlier was talking about liquid biopsy, and then I saw a question from the audience about "are these biomarker tests liquid blood tests or [00:57:00] tissue tests?" And so just wanted to make sure everybody knew that these kinds of biomarker tests where you're looking at the DNA of the cancer to see its molecular makeup, they've more traditionally been in solid tumors, tissue tests. And more recently they're starting to be - healthcare teams can get more information, even just out of a blood test. Not as much as they can out of the tissue test, but in some cases it's impossible to get more tissue. And so there are some cases where the blood test, which is called "liquid biopsy" even though it's not a biopsy procedure, it's a blood test that helps you find out particular biomarkers and what your test results are for those biomarkers. But I'll go back to what Dr. Bauer said where that communication with your healthcare team and really making sure that you have a team that you can talk to, that answers your questions. Cancer Support Community on our help line, we have a program where you can even sit with one of our help line counselors and think through "what questions do I need to ask my team so that I understand what's going on, so that I can help make informed decisions if they're asking me to help decide in treatments?" But that communication goes a long way for you understanding what's going on, and for your healthcare team to also understand what your treatment goals are, and so what would be the best treatment for you.

Ed Kim: Todd?

Todd Bauer: So first, I want to - I know we're getting to the end of the hour, and I want to thank everybody who's joined. And Gina, Claire, Eric, and Ed, great job. Amazing answers. I feel honored to sit on the panel. I guess my take-home points would be that I've seen a number of questions scroll through about fear and should be afraid of genomic testing or should be afraid of this cancer. And my wife is a pre-K teacher and tells me I should never hang out with four-and-a-half and five-year-olds because I don't do kid gloves well. Yes, cancer is something that we should be afraid of, but learning more knowledge about cancer should never be a scary thing. We want to understand as much about that cancer as we can so we can best tailor treatment to those patients whom we care so much for. And whether it is we do the testing and we still go forward with chemotherapy and immunotherapy or we do the testing, we change points, that two to three-week turnaround doesn't change the outcome from that patient. And I [01:00:00] would submit it's well worth it if we're able to put that patient on a better therapy for their disease, specifically for them. And the follow-on to that is well, what are the standard therapies available if it's a sarcoma patient and they have an out [AUDIO SKIPS] fusion? Well, your doc can probably argue that with insurance, though it's a brutal battle in those peer-to-peers. But the next question is "what clinical trials have you looked at for my cancer?" And if you are not asking your provider about what clinical trials have you considered, that's something that I think you can step up and do. Not all docs have time to think about it. Not all docs have time to consider it. I'm blessed in the phase 1 unit, Sarah Cannon in Nashville having access about 200 clinical trials, so I can find something. But the goal is finding something on clinical trial that makes sense for that patient. And this, whether you call it next-generation sequencing or comprehensive profiling or biomarker testing, the molecular understanding of your cancer, just your cancer is the most important thing that you can come away from this with.

Ed Kim: Gina, 30 seconds.

Gina Hollenbeck: Well, I'd say I'm on the spot now. You guys are all rock stars, so thank you so much for inviting me to be a part of this panel. But my first thing would be test, test, test. Find out all you can about your cancer. Always start with the least invasive, which is liquid biopsy. And if it says there's nothing there, that doesn't mean there's nothing there. So then if you have the opportunity to test tissue, then test tissue too. Do them both if you can. If you have the opportunity to do that, then you should test, test, test. And then when it comes to fear, the truth is with having absolutely no risk factors, it was an absolute shock to me to have stage 4 lung cancer. And the fear is real. And so it's OK to be fearful, but also to have hope. Because right now we're getting closer and closer to discovering things, possibly even cures for cancer, and we've never been closer. There's more things coming down the pipeline every day. So my advice would just be to never, never give up and have hope. Not false hope, but informed hope.

Ed Kim: Well, I think that's a great way to finish. Words that I heard today that resonated included clinical trials. The best medicines are being studied now. Wait for your testing. Patient advocacy. Find those advocacy groups. And hope. A lot has changed in cancer, and I think those are real words that we can live by. So we're out of time. I want to remind everyone today that if you want to watch this webinar again, it'll be available on Webinars On Demand page of curetoday.com in the coming days. You guys have been great. I want to thank our panelists and the audience for attending. [01:03:00] Love the questions. Love the dialogue. I also want to thank Cure, Lilly Oncology, and our partners, Cancer Support Community and ALK Positive Inc. for making this possible. And everyone, don't forget to check your email tomorrow for the survey, because you might win one of those gift cards. And again, thank you everyone for attending, and we'll see you next time. Have a good evening.

Eric Nadler: Thanks, everyone. Bye.

Gina Hollenbeck: Night.

Todd Bauer: Good night, everybody. Thank you for your time.

Eric Nadler: Good night.

Claire Saxton: Thanks so much. Night.