EDUCATED PATIENT Lung Cancer Webinar: Midwest Region

Lung cancer is the most common form of cancer in the United States and is the deadliest. However, the lung cancer landscape is evolving to meet the demands of the disease and find new ways to detect, prevent and treat lung cancer.

On Thursday, June 4th, CURE® gathered top experts in the field of lung cancer for an informative lung cancer webinar focused on topics that were highly relevant to patients, caregivers and advocates, including current trends with lung cancer diagnoses, COVID-19 symptom overlap and minimizing risk, biomarker testing and more.

Panel faculty include:

Leora Horn MD, MSc

Associate Professor & Clinical Director, Thoracic Oncology Program at Vanderbilt University Medical Cancer.

Jyoti D. Patel, MD

Professor of Medicine at Northwestern University.

Allison Schaffer

LCSW Private Counseling Practice

Lung Cancer Research Foundation Patient Educational Programs Review Committee

Transcription:

DR. LEORA HORN: Hello, everyone, and welcome today to the live broadcast Cure Education Patient Lung Cancer Webinar. I am Dr. Leora Horn, an associate professor at Vanderbilt University Medical Center here in Nashville, Tennessee, and I'll be your moderator for this evenings' event. We're pleased to bring you this webcast presented by Cure and sponsored by AstraZeneca and The Lung Cancer Research Foundation. I have a couple of important announcements before we begin.

First of all, this webcast is designed to be interactive and we encourage you to ask questions during the event. You can submit questions by typing it in the Q&A box which can be found at the bottom of your screen. If you have any technical problems viewing or hearing this presentation, please click on the question mark help widget in the doc at the bottom of your presentation window and we'll be taking questions and answering them throughout the hour.

I am pleased to be joined today by Dr. Jyoti Patel, Professor of Medicine at Northwestern University in Chicago, Illinois. The place that we normally go around this time of year to see ASCO. And someone from my own backyard, Ali Schaffer, a licensed clinical social worker and member of the patient education program through the view committee at the Lung Cancer Research Foundation. Thank you both for joining me today.

So, there has been a lot going on in the world with COVID-19 and also, recently, at ASCO with the updates that we had on our lung cancer patients. And maybe I'll start with you Jyoti. And just thinking about ASCO and what we saw this past week, if you could pick one presentation, I think we'll get to a lot of the data. What was the one thing that you were most excited about to see at ASCO this year?

DR. JYOTI PATEL: So, certainly, leading up to ASCO, it's been a pretty exciting time. We know there have been multiple sorts of press releases and drugs that were approved in May. But really, I think the one is the single study that was so impactful to patients is the use of adjuvant osimertinib in the ADAURA study. This is a complete paradigm change for our patients. It really brings targeted therapy to the curative setting for a subset of patients.

DR. HORN: So, yeah. So, I think I agree with you. I was very excited about ADAURA. And just to remind those people who are on the chat, it was a randomized phase III trial that was comparing osimertinib after chemotherapy to placebo in patients who had EGFR mutations. And what the study showed us was that there was an improvement in disease-free survival for patients who got osimertinib. A very significant improvement in disease-free survival. And we're waiting to hear about the overall survival data. And Ali, you do a lot of work with patient groups and patient advocates. Do you think it's enough for an oncologist to go to their patients tomorrow and tell them we've got a drug that is going to prolong your disease or prolong the time until your disease comes back? Or do you think that patients are going to say, wait, I’m not going to do this because it's meant to help increase the chance of cure and we don’t have that data yet? What should we be telling our patients? How should be thinking about this data?

MS. ALI SCHAFFER: Yeah, what a great question and I think it's a collaborative conversation. And so, the medical providers who bring their expertise of what they know and what has just been released through ASCO. And the patient can bring their expertise of self and what's important to them in their own life to have a discussion. To share information, ask questions. So, at the end of any kind of conversation, a - - feel empowered with information to make what makes them feel like an informed choice instead of - -. So, I think - - is the providers who help patients understand how this data applies to them and their particular individual medical - -, medical risk. To give them support and - - them decisions. Also, provide that there is a time-sensitivity of the - -. That can be a really helpful factor as well. [audio issues]

Patients feel there is an urgency to make decisions when that's not always the case. So, as a provider, you could improve that. This is something for you to think about and you have the amount of time, if not urgent or this is something that you really need to consider and decide within that couple of days, for example. But knowing the timeframe, you can provide a lot of important - - patients to make decisions and also, to follow up when they have additional questions.

DR. HORN: So, Jyoti, I have two interesting questions in the clinic on Monday and I’m curious to see how you're going to answer these questions. So, one was from a patient who saw the ADAURA data, but she's about a year out from finishing adjuvant chemo. And she asked me, "Do I need to go on this now?" So, what would you tell her?

DR. PATEL: So, this is really tough. So, just to remind everyone. So, the ADAURA study was looking at patients with resected lung tumors and they got up to three years of osimertinib and osimertinib is the TKI that we know that is approved in the frontline setting. The study allowed for chemotherapy and we think that chemotherapy is the standard of care after surgery for patients with stage II and III disease and certain patients with stage 1b disease. So, all of these patients were - -. The primary endpoint of this study was looking at patients with stage II and III disease. And remember that these patients are at a high risk of relapse. So, I think lung cancer is always tough when we talk about it. Yes, it was in an early stage. To even with stage I disease, up to 30% of patients will, unfortunately, suffer a relapse and the stakes are pretty high.

We've shown since the early 2000s that chemotherapy after surgery decreases that risk of relapse, but honestly, those gains are somewhat small when you sort of see new gains with recent trials. But those gains include survival benefits anywhere from about 3% to about 12% or 13% in patients with more advanced-stage disease. So, like stage III disease. What we saw with osimertinib after three years was that we decreased the risk of recurrence so significantly. So, for patients with 1b disease by something we call hazard ratio 0.5. So, that means that - - recur for patients with stage III disease. Where the likelihood of recurrence is almost 70%. That reduction in risk was almost 90%. So, really positive studies.

And so, the trial was designed such that patients needed to start one of those drugs, I think, within 10 weeks of completion of surgery or after chemotherapy. And so, certainly, that year window is out. We know that the risk of recurrence is highest in the first two years, but it doesn't drop off completely. There’s still a risk of recurrence over two to five years and then at five years, we think it's generally new cancer. I think they are astoundingly positive studies. I understand exactly what you were saying. Like that's a tough question. So, are they outside of the window of greatest risk? And at this juncture, are we just adding osimertinib and adding toxicities? And the toxicities are mild, but they're there every single day. You're taking a pill that causes some fatigue and rash and diarrhea. And so, where is that piece?

We know that recurrent disease, though very treatable, can be devastating, right? So, a disease in the brain, disease in the bone, any symptomatic disease can be really difficult. And so, I think it’s a very weighted conversation. Honestly, Leora, for someone with early-stage, so 1b. Certainly, I think I would be less inclined to prescribe it. But in someone with stage III disease where the risk of recurrence is so significant, it may be reasonable to consider. Currently, it's not FDA approved, so, you can't get it, unfortunately, but I think it's something that's certainly emotionally compelling to me despite the lack of data there.

DR. HORN: Yeah. So, we had a long talk that it's not in that approved indication. This patient was 2a and so, we kind of settled on 17 months post-surgery and you're 12 months post-chemo. And I think at this time that we could do more harm than good. And so, I said let's just kind of wait because we also don't know how it impacts the long term chance of cure. And at this point, you're already halfway through where you would have been, potentially, on osimertinib.

So, I guess the other tough question that I had and maybe Ali, I know that you're not a physician, but you do have great insight into what patients are thinking about. I had a patient who was alk-positive, so not EGFR, would not have qualified for this trial. Who is finishing adjuvant chemotherapy and we've talked about the ALCHEMIST trial for them. And the ALCHEMIST trial is the big cooperative group for all that's comparing crizotinib to the standard of care for patients who are ALK-positive. And he turned around and said, "Well, shouldn’t I get one of the better alk-inhibitors like that ADAURA study, and shouldn’t I just go on alectinib because that's what is FDA approved and is better than crizotinib?"

So, as Jyoti mentioned before. Before ASCO, we had selpercatinib approved for patients who are - - fusion-positive. We've also had the approval capmatinib. Finally, we've got something for patients who have the MET Exon skipping mutation in their tumors. What do we do for all these other drivers? Because we're going to have patients asking us those questions and where do we direct patients? What should we be telling them?

MS. SCHAFFER: Yeah. So, that raises the point that chemotherapy or targeted therapy or immunotherapy is one part of a comprehensive care plan. How do you help patients? How do you help families have additional information and support and community? What are the additional actions that people can take that might also support their care? And so, helping them to see what else can you do in addition to some of these treatment regimens? How else can you support yourself and take care of yourself and some of the additional methods? Nutrition, rest, stress management, counseling, emotional well-being, connection to the community, peer support, fitness, movement, exercise, some of the additional therapies. These are also part of the care plans and care regimens. Patients benefit from having the consideration and the conversation and it means a lot when physicians bring in these topics as well. So, patients and family members can understand the importance of these actions, in addition to some of the targeted therapies and how people are making choices.

DR. HORN: Yeah and I don't know about your, Jyoti, but I said to my patient. I said, "I think this is even a bigger reason to go on ALCHEMIST, so we can answer these questions and figure out what we need to do for you after you have finished chemotherapy." I hope this doesn't become a reason the patients don't do chemotherapy because we don't have enough data on substituting chemotherapy for targeted agents or immunotherapy. We know that those trials are ongoing. But hopefully, we're going to get that.

So, other data that we saw at ASCO. You sort of had that perfect segue, Ali, saying immunotherapy and chemotherapy and you know we can not talk about immunotherapy when we talk about lung cancer. And we had some updates. I feel like it wasn't as exciting this year at ASCO for immunotherapy this year, very much my bias. But we had updates from KEYNOTE-189 which was the trial that looked at carboplatin and pemetrexed with pembrolizumab. That got pembrolizumab approval. We had some three-year updates from CheckMate 227 which came just as nivolumab and ipilimumab. It got FDA approval as a first-line option in patients who are PDL-1 greater than 1%. So, Jyoti, with your new patients in the clinic. You now have a multitude of choices. There's not just one choice. When you looked at those trials and I don't know if you want to discuss and help me describe some of those trials to our audience. What did you go with on Monday saying here's what's different and here's what's new what we need to talk about and offer you as a new standard of care?

DR. PATEL: Sure. So, the gates seem, in many ways, wide open and I’m trying to make my decisions less arduous. So, going in ASCO, we had ideas about patients with targeted oral mutations that certainly go on targeted therapy. Patients who are ineligible for those. We sort of look at their PDL-1 status to relegate whether we do single-agent immunotherapy, chemotherapy with immunotherapy. It was relatively straight forward unless someone had a real pushback or quality of life concerns about starting chemotherapy. If someone's number was greater than 50%, they got single-agent pembrolizumab. If it were less than 50%, you could get chemotherapy with pembrolizumab. And there are also other combinations with the atezolizumab, but I think sort of most of us tend to do the drug that was approved first.

So, in the month and days preceding ASCO, there were two approvals in the frontline setting that I think is really important. And what was presented at ASCO was the updated anAlisis of CheckMate 227. This is a trial that has been ongoing, and I think it’s gotten a fair bit of sort of discussion about how the trial has morphed over time. Nevertheless, the regimen that was finally approved was nivolumab and ipilimumab in patients who had PDL expression greater than one. We have seen other dices of this trial and we know that this can be a regimen that's quite active in patients with no expression of PDL and PDL-0. But the FDA approval and the primary endpoint of the trial really focused on this population with some PDL expression. So, that's what was approved.

What we saw at ASCO, I think was really exciting. It was the three-year updates on this regimen and a couple of things to me really stood out. One was that patients who got ipi-nivo and had a good response at six months seemed to sort of plateau for the next three years. So, that early response sort of indicated this prolonged benefit from these drugs. So, I think that's really compelling. There's a subset of patients that do very well for a long time with both CTLA and PD inhibition.

The other piece I think that was really exciting about sort of these regimens. Again, even if we don't look at that sort of landmark analysis at six months. It was the proportion of patients. About a third of patients on ipi-nivo, regardless of how they did, continued with disease control at three years. So, certainly, without chemotherapy, we thought that was pretty exciting in the entire population greater than 1%. I think right before ASCO, there was another approval of chemotherapy with ipi and nivo and Leora, maybe you want to talk about that. Because I think that's what, probably, is most exciting to me. To how to sort of fit this in the paradigm, but the one that's most perplexing as well.

DR. HORN: Yeah. So, that was the non-LA [phonetic] study which looked at chemotherapy with or without nivolumab and ipilimumab. And it showed improved response rates, progression-free survival data compared to chemotherapy. And I think we've had a lot of trials that have shown this. What was interesting to me in that study is the toxicities were really not that high, but patients only had two cycles of chemotherapy with nivolumab and ipilimumab and then continued with the nivolumab and ipilimumab. And so, part of the thought behind that study was could you also-- a lot of the trials that we look at, we see a lot of patients who get single-agent checkpoint inhibitors or even nivolumab and ipilimumab had this rapid progression.

And so, we didn't see the question was could you flatten that curve a little bit in the first two cycles and then maintain the responses with nivolumab and ipilimumab. Someone asked me the other day which combo I’m going to use, and I don't know that I’m going to jump to that, but the answer that I had from them is that we have so many drugs with such similar data. And I said to them, "I'm going to use the one that's least expensive, but they're all the same price right now." But I’m curious to think and get your opinion on this, Ali because I know this probably something very important to our patients. It's important to society really. It's the cost of care. That’s where my Canadian training always comes back to me.

But we've got so much data now showing fairly similar outcomes. I actually would be more excited if the FDA had approved nivolumab and ipilimumab in the PDL-1, 0 patients because that would have given me a non-chemo regimen rather than getting another chemo regimen. So, Ali, did you hear much buzz from folks about these regimens? What are your thoughts about the cost of these different drugs? Because they are fairly cost-prohibitive. I'm just curious about what you thought of the data.

MS. SCHAFFER: Yeah, it's challenging because we can't look at care without looking at cost of care. And yet we never want that to be the driver of the decision making when we are balancing that against someone’s life or someone’s extended life expectancy. So, it becomes a real stress point for patients and families wanting to have a quality of life, wanting to have a quantity of life and also, trying to make decisions when some of these treatments are incredibly cost-prohibitive.

Cancer care is expensive and there are many organizations that are trying to support an offset, some of that funding. But that becomes very real factors in decision making. One of the challenges is for patients to be able to get upfront, true, and static costs of what some of the treatment decisions are going to be and they can't always get that information because there might be changes in cost or ancillary things that come up as they need more, maybe, supportive care as they're needing side effect management. And so, even if they did have some of those static costs of treatment upfront, it doesn’t mean that's what's going to be the case over time.

And so, again, it comes into conversations. What do they have available? What are they willing to do? Talking with insurance providers, talking with their treatment providers. But it's really a hard thing when it comes down to cost and is that going to be the thing that keeps somebody alive or extends someone's life. Nobody wants to have to make that choice based on cost.

So, that's not a simple answer and there's not a simple pathway forward except ask a lot of questions, decide personally what you're willing to do, and what is available to you. And then work with your providing team to make the best choices that you can.

DR. HORN: Yeah and it's amazing to me to see how well our lung cancer patients are doing. People are living for a long time and so, it's not like you can budget for a six-month illness and stage IV disease. Because now, patients with stage IV disease. I have some patients in a decade. That's because I’ve only been practicing on my own for just a decade. And it's just so good to see them and hear about their children and their grandchildren and their lives. When people come and you're not talking about cancer therapy for the entire visit. You know that things are going well. But I’m hoping that what happens in lung cancer is what happened in hepatitis. When we had so many disease drugs for the same indication. We suddenly got drugs that were affordable.

One of the questions that came through was what about immunotherapy for patients with k-ras mutations? Did we see any new data this year? Last year, we saw a really nice analysis from Dr. Skelidus [phonetic] who looked at patients who were getting chemotherapy with immunotherapy. Maybe these patients had k-ras mutations, but maybe they also had LKB-1 or STK-11. And his data showed us that those patients who had those co-mutations. Maybe they didn't do as well with immunotherapy and we need to be thinking about other treatment options. I don't remember seeing any great updates for immunotherapy with the k-ras mutations, but Jyoti, maybe you want to talk about some of the data that we saw with the new k-ras inhibitors that seem to be coming down the pipeline at ASCO this year.

DR. PATEL: Sure. So, certainly, we know that k-ras mutations are quite common and that there are a number of different subtypes. The most common k-ras mutation that we see is G-12-C. And so, there has been, I think, for the past year, multiple presentations about AMG-510, as well as some smaller ones about IM/RADI compound. These are oral drugs that appear to have really good efficacy. The numbers are small. I think questions about the durability of response remain. This year at ASCO, we saw AMG and other tumor types. So, we saw some responses in small cell, as well as in colon cancer. An idea that this is a legitimate pathway, but also, understanding that perhaps these drugs are less effective in colon cancer than in lung cancer. And it may be because of downstream pathways. So, certainly, I think there's a lot there to continue to learn about and we'll see what some of these registration trials look like.

There was some information about STK, and these are the numbers that we get. On most of our mutation panels, we have a lot of mutations and we think that we may be able to understand the immune response. I give STK as part of my panel at Northwestern and I think most commercial vendors give it as well. Thus far, I have not used it as assigned therapy. I've used it as part of a clinical trial. There were a couple of studies suggesting that STK and other mutations may be more prognostic than predictive of response to certain drugs. So, it may be that these similar mutations make the response to immunotherapy less effective, but I think it needs a lot of further study.

So, at this juncture, if someone had an STK mutation, I wouldn't hold immunotherapy. I don’t feel like I have enough information. I think it would be - -.

DR. HORN: Yeah. I wouldn’t hold it, but I’m more likely to give it in combination with chemotherapy. That's sort of been the way I’ve looked at those reports that we get on our patients.

DR. PATEL: I absolutely agree with that.

DR. HORN: One of the other exciting presentations that I think I’d put up there in my top five, although, it wasn't in the lung session. It was the antibody-drug conjugate in the DESTINY-1 trial. And I know I’m going to butcher this name. Trastuzumab or deruxtecan. Or I’m sure we're going to come up with a nice short form for it. So, we got excited a few years ago about DLL-3 and ADC with Rova-T. That looked good in phase I, but it seemed to have these toxicity signals and fell apart. But the DESTINY-1 trial looked at this agent that is currently approved in breast cancer patients. So, I feel like we've got more safety data and it looked in patients with HER-2 mutations. And we saw a response rate of over 60%. We saw a PFS of around 14 months. Is this something you're excited about that you think that we're going to see more of? This was in a combined GI and lung cancer patient population, so small numbers. It was the second line. It wasn't first. But have we finally got a targeted agent for HER-2 positive patients, do you think?

DR. PATEL: HER-2 mutations have been really tough. Often, they are lumped in these clinical trials with EGFR Exon-20. What we've seen is most of the TKIs that have been tested are minimally effective, come with toxicities. It's a tough nut to crack in many ways. So, certainly, I think we are really excited about this ADC.

There was pneumonitis in the study. A little bit more than we usually see, about 5%. So, I think that needs to be sorted out. The numbers were small, but certainly, how great to have a drug for this distinct subset and I’m anxious to watch it move forward in larger trials.

DR. HORN: And I’m quite curious to see, for those patients who got pneumonitis, had they got immunotherapy before. And so, is it a combo or the ADCs with the chemo? Ali, should be trying to advocate to get this drug for outpatient when it's not FDA approved, or should we tell our patients to hold your horses? I actually had an HER-2 positive patient in the clinic on Monday who's on a clinical trial and I kind of mentioned the ASCO data because I spent the whole weekend watching Zoom with my kids, ASCO on Zoom. And so, what do you think we should do for our patients with this drug, or do we still need to wait for more data? Oh, Ali, I think you’re on mute.

MS. SCHAFFER: I am, thank you. Any time there's an opportunity to advocate on behalf of treatment regimens. That there is data to prove it or sufficient things to say we need more. Absolutely. Taking that approach of advocacy with all of the different avenues that you have. I think it brings the point that patients and families are hearing some of this information. They're getting excited and they're getting really hopeful. And that's a huge thing. It's there's hope associated with some of these new regimens. And then it's also taking away that hope and feeling pretty heartbreaking when they hear, "Oh, but we can't get it," right.

So, I think it is a really important thing to be aware when you offer a potential treatment regimen that's not actually available. How that might be impacting the emotional wellbeing and the hope of a patient and the family of what might be available. Because what they're invested in is their life. They want to live, right. Patients and families are involved with the treatment and doing these things because they want to live. And so, hearing that there's a treatment that's not available to them that might actually serve them is a really hard place to sit for a patient. So, anything that you can do as physicians to advocate and to create access to this treatment is incredibly important and I would say yes every time.

DR. HORN: Yeah. I think another reason to keep encouraging our patients to go on clinical trials. And I feel like in the lung cancer community we're very lucky. It's a collaborative group and if we hear about something that's better than what we have down the road or across state lines. If you're allowed to cross the state lines right now, then I think it's a reason to send those patients. So, Jyoti, we have a question from a patient. If someone is exhausted their TKI options and their PDL-1 score is zero, do any of the new approvals apply? So, should that patient get nivo and epi or should they get chemotherapy with nivo and epi? What can we offer? Because we've heard a lot. We've seen data out of some different institutions showing that patients who have driver mutations maybe don't derive as much benefit from treatment with checkpoint inhibitors. What would you tell this patient? What would you recommend?

DR. PATEL: Sure, it's tough because we really don't have very much data. So, we know it's single-agent PD-1 inhibitors or PDL-1 inhibitors, the response rate in patients with the driver mutation. And not all driver mutations. Let me sort of step back a little bit and say EGFR, all, and ras-1. We have pretty good data about it. But their response to single-agent immunotherapy is less exciting. A couple of years ago, Matt Hellmann presented data with epi and nivo in patients who were sort of post-TKI and there was certainly some feeling that some patients with EGFR mutations who had progressed were having responses. Honestly, I think as that data has matured, many of us have felt that maybe that was just early numbers and hasn’t matured as nicely.

It's tough, also, because the FDA approval for carboplatin, pemetrexed, and pembrolizumab excluded these patients and we know that carboplatin and pemetrexed are sort of a backbone for patients after the failure of TKIs in patients with driver mutations. So, we've kind of been left with the only real data we have which is a combination of carboplatin, paclitaxel, bevacizumab, and atezolizumab in these patients. And certainly, we know that the addition of anti-VEGF with bevacizumab plus atezolizumab improves outcomes in this subset of patients. The improvement is, I think, a little bit more modest and the numbers continue to be small, but this is an area of active investigation.

So, there are a couple of trials right now that are looking at these particular populations to better define what response would look like and whether or not we could sort of switch chemotherapy backbones. So, I’m optimistic that we'll have more agents. Currently, what do I do off of a trial for many patients? For a patient with an EGFR mutation, often I'll actually continue the osimertinib and add chemotherapy, sometimes, with or without bevacizumab. It depends a lot on what burden of disease they have. Generally, I think our paradigm has shifted a lot in the past several years. If a patient develops resistance, we try to do another biopsy to understand the mechanism of acquired resistance and whether we can use two targeted therapies to overcome that resistance or whether or not systematic chemotherapy is appropriate, and then we sort of add on to it. Sort of the paradigm I have is that really we want to think about the longest time that we can have disease control because the science is evolving so rapidly. The cadre of clinical trials and our early discovery of understanding mechanisms of resistance is changing dramatically in years.

So, even if a patient can go on chemotherapy for a year or so on a regimen that's effective and has low toxicity. And yes, it's a drag getting infusion therapy after you've been on oral chemotherapy, but if we can get even a year. I'm optimistic that the science evolves in that time and certainly, we're seeing that more and more with the number of agents that we're bringing from VEG to bedside.

DR. HORN: Yeah, definitely and you know what? I always worry about when I give a patient with a mutation, a checkpoint inhibitor. When I want to give them another TKI because there's something newer or better, they might add more toxicity to that TKI.

So, Ali, as Jyoti mentioned, we're looking for a longer time with disease control because lung cancer patients have such a better prognosis. That's always the first thing I tell my patients. So, as someone who's working with people who are impacted with cancer, who are specifically supporting their emotional wellbeing, what do you want people to know? What's important for people who are listening to us today to think about for these patients?

MS. SCHAFFER: Yeah. So, hope is one of the things that first come to mind. How important and how personal hope is. That hope means something different to every person. And so, for all of the healthcare providers, as well as the families and patients living with and impacted by lung cancer to really be willing to bring hope into the conversation and into the care plan and into their daily lives as a way of coping with a cancer diagnosis.

Let's be clear, cancer diagnosis, at it's basic, is a life disruption and it has various implications and magnitude for each individual. And there is likely going to be an emotional impact. It doesn’t mean that someone can't develop coping mechanisms and skills to deal with and respond to the impact of a cancer diagnosis. But I think as someone who is a clinical social worker, again, working with people around emotions. Every day I’m helping people learn how to feel their feelings around a diagnosis, how to create their own roadmap for what it means to stay engaged in care and to develop coping mechanisms to help them tolerate treatment, help them stay engaged in day to day life, and having a meaningful quality of life and meaningful personal connections.

So, another thing I’d like to really remind people of is the power of community. So, tonight we're all coming together to share information, to ask questions, and I want to remind everybody that there is a lot of incredible online support and personal support about the lung cancer community. As a representative of the medical advisory review board with The Lung Cancer Research Foundation, I know they're one of the organizations that are doing a lot to fund research, to provide access to information to patients and families. They have peer support, peer mentors. So, both caregivers and patients. And in addition to The Lung Cancer Research Foundation, Cure Magazine is a huge wealth of information and community. So, there's so much out there and available and I want to remind people to use the connection of community and use the connection to information for their own wellbeing and for their own care of treatment decisions and quality of life.

It's so important that we look at the broader scope of care to include all of these aspects and I want patients and healthcare providers to leave feeling empowered. That they have the ability to participate to make change in individual lives and that it really does matter.

DR. HORN: Absolutely and-- sorry, go ahead, Jyoti.

DR. PATEL: I was going to say it's so important for us to realize. Like these past months for all of us have been so disrupted. Sort of the communities that we surround ourselves with, all of our bolsters, and our emotional wellbeing. Sort of even that physical sense of being close with people has been so disrupted and this can be a lonely disease and I think during this pandemic, it's even lonelier. One of the most important studies I actually want to highlight. Leora got to present sort of an international collaboration that she's leading, looking at the effect of Coronavirus in patients with thoracic cancers. And that kicked off all of ASCO, right. I mean it was one of the most important pieces. The pandemic disrupted not only our lives but also, this great meeting. So, Leora, do you want to talk a little bit about that?

DR. HORN: Sure, and I can probably answer one of the questions that came up about our lung cancer patients before COVID. So, when the pandemic started, we didn't know how long this was going to go on for. And so, we were sitting here in the U.S. waiting. I feel like we're sitting in Nashville a little bit, still waiting to see what happens. But Marina Garassino, who is a lovely medical oncologist in Milan, sent an email out to 50 of her friends which I think goes to show the collaborative environment of the lung cancer community because there's not a lot of groups that could do this the way it happened. And she said, "That what's happening is terrible for our patients. Not only am I worried about how they are doing, but I’m worried about delaying the care and we need to collect data."

So, we were here in Nashville and I said, "Well, clinics are half-closed, and I can't get people to come in and we can do this. We can collect the data." And I hope it's a lesson to companies for future clinical trials because within two days, we had established a case report form and within a week of us deciding to do it, we had IRB approval at our university and Italy actually had IRB approval for a whole country. And within about six weeks, we had collected data on 400 consecutive patients who were diagnosed with COVID and lung cancer. And now, I don't want people to hear the data and be-- I think there's a concern, but I don't want it to be the wrong sort of concern. And what we found is in patients with lung cancer, who developed COVID-19, the mortality was much higher than what we expected and higher than we've seen in other tumor types. CCC-19 is another collaboration that's ongoing across The U.S. They had data on about 100 patients presented at ASCO, about 100 who had lung cancer. And they had about an 18% mortality and we had a 35% mortality in our patients.

We're looking at what were the risk factors associated with mortality? The average patient was over 60 years old that was enrolled in a database. The majority of patients which was really surprising to me either had not been treated. So, they were getting diagnosed with lung cancer at the same time as they got COVID. Or they were on their first-line therapy which meant that their oncologist thought that there was a good reason to be on treatment and that there was hope and options for those patients. So, it's not like these were patients who were sicker from their lung cancer and later line therapy.

We found that patients who were older, over 65, who were maybe not as quite as fit. Who were on higher doses of steroids and who had either chemotherapy by itself or chemotherapy with immunotherapy. They were at higher risk of dying from COVID.

Now, I think there are two important messages that came out of this. One is that we need to be concerned about our lung cancer patients, but I think, importantly, we need to realize this initial group of data was at the height of the pandemic in certain cities. Definitely in Italy, definitely in France and Spain where some of this original data came from, as well as some sites in the U.S. such as New York.

We're now up to over 600 patients and our goal is to get over 1000 to better understand some of this and we're starting to see in screens some of the asymptomatic patients at our centers. What it said to me is we must stop giving our patients the first best therapy. If we think that chemotherapy is going to be beneficial for our patients. If we think chemotherapy and immunotherapy is the right treatment to do, don't forgo the chemotherapy and just give the immunotherapy. Because sometimes, we've got one chance at really controlling the disease, but we need to minimize the patient's interaction with the healthcare system. So, don't bring patients in for weekly labs. They don't need it. Let them come in once, get their treatment, go home, follow up on the phone, follow up on telehealth, follow up however your different institution is able to do it.

But I think that we still need to offer our patients the best level of care. What we've seen in The Netherlands which is scary, and I think we're going to see the same thing here. It's that the number of patients going in for screening has decreased and that is a big concern. Because last year, we had improvements in cancer mortality, specifically, due to lung cancer. Are we going to see worsening cancer mortality when we get lung cancer statistics in the next two or three years as patients delay care? And I do worry about that, but I think what - - did tell us is that our patients are at risk. When you get chemotherapy, you should continue social distancing even if your city or country is opening up. You should continue to be careful. You do need to be that little bit more rigid in how you're living your life right now. Because to beat cancer so to speak or get that cancer under control. To die from this virus just seems so not fair for our patient population.

Ali, what are you telling patients who are worried about going to their doctor? And Jyoti, Chicago is not like Nashville. We have no public transit. You probably have a lot of patients taking cabs and public transit to get to Northwestern. What are you guys telling patients out there from the - - data?

DR. PATEL: So, certainly, our experience at Northwestern has been that we've actually seen very few patients with lung cancer and COVID in Chicago. I think we really did a great job of flattening the curve. Although we had a big spike, it was much less than projected and I think social distancing has worked. I'll say over and over many of us in healthcare or parts of clinical trials. I'm getting my serology tested often. I'm high risk of going to the hospital. I've volunteered in the inpatient service. I think in the hospital and at points of healthcare, I actually feel we're quite safe because there's a code of conduct. Everyone is screened for symptoms. There's hygiene. People wear masks. And so, my message to patients is that if you need care, you need to come to the hospital because it's actually a pretty safe place.

The other piece is sort of the silver lining of all of this. I think we've gotten much more creative in how we deliver care. It's much more patient-focused. Patients come to the hospital at points of need. I'm not doing extraneous visits and blood tests if patients don't need something from me or don't need an intervention. Incongruent with this was also that we had some changes in the FDA label for the dosing of certain immunotherapies. So, suddenly that could be atezolizumab and durvalumab. In small cell longer cancer, it can be given every four weeks instead of every three weeks. So, certainly, I think there's an effort to streamline care. The FDA has issued a bunch of guidance about clinical trials. We may be able to get blood draws and imaging at such sites off of the study site.

So, I think there are a lot of things that will come from this that are much more patient-focused and will make trials easier to do in the long run. But I think our immediate crisis is how do we keep people safe? How do we assure people if they have symptoms, they need to come to the hospital and engage with medical care? Because I actually think right now, most of the hospitals are pretty safe.

DR. HORN: Are you swabbing? We're swabbing patients before they start any therapy. Are you doing similar things at Northwestern right now?

DR. PATEL: We are. So, patients are tested before procedures and at the start of therapy.

DR. HORN: Ali, what are you hearing from patients? What are the big questions? How can healthcare providers support the patents? How can the patient's families support them during this time?

MS. SCHAFFER: So, there's a lot of uncertainty and uncertainly equals a lot of fear. And so, some of the ways that I’m recommending. What are the ways to reduce that fear? And one of those things is get informed, get accurate up to date reliable information. And then do the due diligence to check it out with your healthcare providers, right. That's what you are here for. It's to help patients to understand their risk, understand care protocols, understand the potential impact when some of these care protocols might change, right. Because even when a patient is used to having a certain dosage or a certain timeframe of the treatment regimen, that becomes security, right. And then when you switch that, that can inadvertently increase fear into stress. And so, it's really important for patients to ask how might this change either my quality of life or my survival? Or what is going to change?

And so, conversations and communication around the information. Whether you're reading studies online, whether you're hearing things. Because the cancer community is so connected, so patients are also hearing information from each other about what's happening where they live. And as the two of you who are working in reputable institutions in different states, you're even checking out what are you guys doing? Are you swabbing or are you not swabbing? So, I think that even raises the point that patients might be hearing different things based on where other people are sitting in the world and it's still critical to bring it back to their healthcare providers. To check it out as it relates to their institutions, their care teams, and their personal history. That will help reduce some confusion and ideally, also reduce the fear associated with the uncertainty and the unknowns.

Because what I’m hearing in this conversation today is how much the two of you are tapped into up to date information. And so, I send all the people I’m working with to talk to your healthcare team if you have questions, whether you're in active care or not, follow back up with the people that are going to specifically answer it as it relates to you.

DR. HORN: Definitely and I think I’m always looking out for those updates. So, Jyoti here's a question that came through. For a patient who is on keytruda or pembrolizumab and they progressed, should they avoid chemotherapy? Clinical trials are sparse right now. Slowly, a lot of companies shut down their trials. They are slowly opening them up. What second-line treatment would you offer them and is chemotherapy a bad idea and they should stay with pembrolizumab?

DR. PATEL: So, certainly, if the pembrolizumab is no longer working or the atezolizumab is no longer working, then I would advocate for trying something else. And although chemotherapy for someone who's been on an oral agent, immunotherapy is really daunting. It's quite effective and in many patients who have a good quality of life, minimal fatigue, minimal toxicity from chemotherapy. And it may be as sort of a bridge to the next treatments. Often, clinical trials will recommend immunotherapy, as well as a platinum treatment prior to enrollment on a clinical trial.

Although medical research has stalled, large lung cancer trials have continued because often, being on a clinical trial is the best available option or the best therapy. So, I think those will be prioritized at most institutions to open up. But certainly, I think chemotherapy can be effective. There is a large effort now called the INSIGNIA trial in which patients with some PDL expression either get pembrolizumab and then switch to adding chemotherapy to the pembrolizumab if it doesn't work or completely switching onto chemotherapy alone and forgoing further pembrolizumab. So, certainly, I think we'll have clarity around these in the next years, but definitely a work in progress.

Understand, also, that we have, I think, a couple of years ago talked a lot about pseudo-progression and the patient who was having evidence of cancer progressing may actually be benefitting and to just be patient. I think putting someone onto something because it's comfortable and not working is probably not serving anyone that well and probably the number of patients who have pseudoprogression is really benefitting is quite small. So, I would say take the plunge and consider it and more clinical trials to follow.

DR. HORN: Definitely and we had a similar question from someone who said they are responding to pembrolizumab. What comes next? And they have 100% PDL-1 expression. I'm hoping that you don't need the, "What comes next," but I think Jyoti covered that. We don't have a lot of time, but the last thing that I wanted to cover because it's something near and dear to my heart to where I live is small cell. And we had some updates at ASCO for patients who had small cell lung cancer. We had updates from the CASPIAN study. This was a trial that looked at chemotherapy with or without durvalumab for patients with small-cell lung cancer. There was an update for patients who had brain metastases that were untreated, and the trial showed us that durvalumab did have a benefit in those patients even if they had untreated brain metastases. And we also had updated data from KEYNOTE-604 which was a randomized phase III trial that looked at chemotherapy with or without pembrolizumab which showed an improvement in progression-free survival, but there was not an improvement in overall survival.

When you looked at ASCO, did any of this sort of change you're doing for your patients with small cell lung cancer? If they present and have brain metastases, it's a tough one. Are you recommending not to radiate? Let's do chemo and see what happens. How are you approaching those patients after ASCO, Jyoti?

DR. PATEL: So, certainly, I think we finally changed paradigms with patients with small cell lung cancer over the past year or so. So, with the durva data, I’ve been enrolling patients with clinical trials or treating patients with brain metastases with durva front. I think the data is now a little bit more grounded and I feel quite comfortable treating those patients. I think sort of the takeaways for me in small cell was that although the pembrolizumab trial was negative, the curves looked a lot like what we've seen with other regimens. And so, I think IO and chemotherapy are effective for this group of patients. I think it was probably a statistical issue or maybe a little bit of bad luck that the trial wasn't positive in OS.

The other piece was that in CASPIAN - - in combination with the durvalumab. It was a negative trial. And in fact, I wonder if we actually hurt some patients with the addition of the fourth drug. That's tough because we know - - inhibition with PD inhibition - - certainly, a group of patients that have long term survival. And so, sort of figuring out when these drugs should be given, I think, still remains to be seen.

DR. HORN: Yeah. So, that was sort of a question that came up in the clinic when I was talking to my research nurses. Because the ADRIATIC trial is open. And what the ADRIATIC trial is, is a trial that is giving patients chemoradiation for small cell. And once treatment is finishing, they're either being randomized to receive placebo, durvalumab, or durvalumab and tremelimumab. And what we're hoping to see from this trial is the same benefit that we saw in non-small cell lung cancer. That really led to the approval of immunotherapy for a year after treatment.

Ali, do you think patients will have a reservation about getting durvalumab and tremelimumab now seeing that the CASPIAN study was negative? Or do we say, well, that was with chemo, so we still need to look at this question because we don't have the answers? Or are people talking about the small cell data? Have you heard any concern in the cancer community?

MS. SCHAFFER: People are talking about it because, of course, there are questions. As you pointed out, there's not a clear answer. There are still questions. And so, again, it comes to talking. I feel like I keep saying this, but it's really the most important thing. It's to be in close communication with your healthcare teams. To be making decisions based on your personal history, your personal risk factors, and your personal responses. What's the best choice or what's the choice that feels most aligned for where you're at and what you're trying to accomplish and what the goals of care are. So, there's always going to be questioning when there's no one way. And through conversation and communication and close monitoring, I think those are the best ways to create the path forward.

DR. HORN: Absolutely and Jyoti, I think we got time for one more question. So, speaking of the PACIFIC data and looking at the osimertinib data for patients who got chemo and traditional therapy, should we be thinking about osimertinib for our patients who got chemoradiation therapy because they're such high risk? There is a trial that is ongoing. It's amazing to me how quickly immunotherapy trials close and open. And for a while, I feel like there was TKI. Just fatigue or less excitement. And suddenly, we’re excited about TKIs again. I'm excited about anything with lung cancer really that moves that curve forward. And so, what do I do with my patients? Do I say, well, we don't know, so let's keep up with the durvalumab? Or should I talk to my patients about this again? As Ali mentioned, it's not an FDA approved indication. We don't have the data yet.

DR. PATEL: So, certainly, in PACIFIC, the number of patients with the EGFR mutations was quite small. We didn't know it for a huge proportion of patients. It looks to be a trend, but it's a really wide confidence interval. I guess mechanistically, to me, it makes more sense than probably a TKI should be appropriate there, but we don't have the data. And in fact, when we looked at a TKI after chemoradiation in unselected patients, we actually hurt those patients in an older - - study. And so, my sense is that the jury is still out. Perhaps, I’m less willing or my threshold to stop durvalumab in these patients might be a little bit higher, so you develop a little bit of pneumonitis and I'll probably hold off. But Leora, what are you doing?

DR. HORN: Yeah. I mean I’m seeing the same thing. We don't have the data. We don't know what to do. I know that certain people are jumping on that, but I think we need to wait because we don't want to harm our patients and osimertinib can cause pneumonitis. And so, starting that immediately after could put our patients just as much at risk.

In the last few minutes or seconds, Ali, what are you most excited or most looking forward to for our patients coming up for the rest of 2020 besides a vaccine?

MS. SCHAFFER: Yeah. I think it's really the breadth and the width of treatment options that are available. There's so much possible and that equals longer life, a better quality of life, and all of those things are really exciting. That the lung cancer community continues to have possible options and that's really exciting. That people are putting a lot of investment, a lot of money, a lot of time, and research into the lung cancer community. Because it's an important population of people that deserve this kind of attention and these treatment options. So, I’m excited about all the possibilities.

DR. HORN: Jyoti, how about you?

DR. PATEL: So, I think there's been a sea change in the past few years and it's high time, right. I mean we've put in. Sort if we work on the foundational science, patients have volunteered to be in clinical trials and to work with us. But now, we're talking about really understanding what regimen to treat or the best data we'll have for regimens to treat patients with stage IV lung cancer. It won't be real for five years, right. We're seeing all of these immunotherapies, immuno-chemotherapy regimens, and we have data now at three years. Now, it really depends on what that tail of the curve looks like.

So, bringing better therapies, and really thinking about a longer patient journey, multiple options, holding off on toxicity, and keeping patients well as the science evolves. That's what gets me excited with a really great group of collaborators and I think that's been sort of the story of 2020. It's how people have pulled together during these tough times - -.

DR. HORN: Absolutely and I hope those people listening out there come back to the clinic. We're here to take care of you. We want you to be safe and we don't want you to neglect your cancer care because you have good options. And if you know people who qualify for screening, make them go get that CT scan because screening CTs can save lives.

So, I want to thank our panelists and the audience for attending and participating in today's events. I want to thank Cure and our sponsors, AstraZeneca and The Lung Cancer Research Foundation for making today's educational session webcast possible. And I hope to see you all next time. Have a good night.

DR. PATEL: Thank you so much.

MS. SCHAFFER: Thank you.