Andrew Schorr: Hello and welcome to Patient Power sponsored by the Seattle Cancer Care Alliance. I m Andrew Schorr.

Transcription

1 Immunotherapy Advances in the Fight Against Lung Cancer Webcast June 29, 2012 Laura Chow, M.D. Assistant Member, Clinical Research, Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance Eva Borsi Please remember the opinions expressed on Patient Power are not necessarily the views of Seattle Cancer Care Alliance, its medical staff or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That s how you ll get care that s most appropriate for you. Eva s Story New research suggests there may be a way to reinvigorate your immune system to fight non-small cell lung cancer. It s a big deal. Hear about ongoing clinical trials and meet a patient who s benefitted next on Patient Power. Hello and welcome to Patient Power sponsored by the Seattle Cancer Care Alliance. I m Andrew Schorr. Well, one of the scariest cancer diagnoses is lung cancer, and it has been a tremendous fight with researchers trying to develop effective medicines to help people live longer with this disease. Particularly when it s advanced it has really been a tough go. But there is progress that s being made. You ve probably heard about different medicines, ALK inhibitors, and there are other genetic targeted medicines that have been developed that are showing promise and really helping some people who really had very advanced cancers. But what about more progress? We want more. And so let s hear the story of Eva Borsi, because she s an example of someone in a clinical trial where it s shaping up as a real breakthrough in lung cancer, and we re going to hear about that from her doctor who is a researcher in the field in just a minute. But first let s meet Eva. Eva is just about 48 years old now, lives in Seattle, works at the University of Washington in the dental school and is an avid athlete, I would say, Eva. You would bike to work every day, right? Yes, that s correct. And so you ride--you re one of those cyclists who whizzes by us, and even though you have three daughters you go to the gym and you re not only a parent but you re very active physically, right? 1

2 I m perhaps not as active as I was maybe a year ago, but, yes, I m pretty active I would say. Right. Well, let s talk about what s happened in the last year or so, and that is biking up the hills going home, what did you begin to feel? Just shortness of breath, and it felt like somebody was always sitting on my chest. Very unusual for you. You d never really had any health problems, right? No. I have not been sick at all. On very, very few occasions I had to visit my primary care provider. So you go back to work and you re complaining about this, and your co-workers, what do they urge you to do? To go see my primary care provider to find out why because I m usually never sick and me complaining is something out of the norm, so that s how I ended up going to see her. And she always knew you as being the picture of health, right? Yes. She has been my provider in the last 20 years. Right. So being short of breath can be a lot of things, but at the far end of the list something really bad would be a complication with the lungs and maybe even some complication of lung cancer. She does a chest x-ray just to rule that out, but what happened instead of ruling it out? Well, I had a lot of fluid in my pleural space which caused my lung to be not expanding. There was just not enough room, so I guess that was the cause of my shortness of breath. So they send the fluid to the pathologist after removing that, and what did they find in the fluid? 2

3 Cancer cells, and I guess after further analysis it was determined that it was adenocarcinoma. Right. And you thought, well, if they re cancer cells, I m a woman, maybe it s breast cancer, and it wasn t. You were bowled over to find out that you, as a nonsmoker, not anybody who lived around anybody who smoked, that it was a lung cancer. Yes it was--it was pretty shocking to say the least and surprising, that out of all the wretched diseases that I could have, lung cancer was the one. So this brings you to the Seattle Cancer Care Alliance, and the world-renowned Fred Hutchinson Cancer Research Center. And you re connected with a leading researcher there, Dr. Laura Chow, who specializes in part in lung cancer. So you sat down with Dr. Chow, got all the different diagnostics. So what was the first approach that you tried? Well, first of all, I came basically telling her that I don t have much hope in this, and she said, I think I can still help you given your age and your overall health. Let s just try to do the traditional chemo route and see what happens. Now, we should mention that, as I said earlier, there have been some advances in certain genetic subtypes, but you had those genetic tests, and you didn t have any of those genetic types. Yes. Unfortunately, I was tested negative for most of those known genetic subtypes, so I was not spared from traditional chemo at that time. Which was hard. I mean, I managed, but yes. It was not fun. Hmm. We should mention to our audience, though, you are a tough lady and so you were biking to your chemo appointments. Yes. Actually, the first two chemo appointments, I came to work and went to the chemo center here at the UW up, on the eighth floor, after working half a day and 3

4 going to chemo for the rest of the day. Well, let s meet your doctor because I want to pick up the story in what could be a real breakthrough in the treatment of non-small cell lung cancer, and that s Dr. Laura Chow, who I mentioned. She s an assistant member in clinical research at the Fred Hutchinson Cancer Research Center, and she sees patients like Eva at the Seattle Cancer Care Alliance. Dr. Chow, so here she does not have the genetic subtypes that we had other medicines for but you did have one spot in all of North America left for Eva to be in a clinical trial, and this was for an immunotherapy approach. So, first of all, what is immunotherapy? Well, let s start off a little bit with background on the approach for Eva-- for most of our lung cancer patients if they re nonsmokers and they re fairly young and fit, the best possible scenario usually is to find a mutation so we just are able to treat our patients with a pill and they can have responses that last for a really long time. So that s always our first hope when we are trying to treat patients with lung cancer, and we actually think that targeted therapy is a bit of a miracle and it s always our first step. And this is--i mentioned like the ALK inhibitor and some of these. And the EGFR inhibitor, so at this time we re trying to do more and more mutational testing, but, I was really disappointed because we wanted to offer something to Eva and unfortunately she was negative for any of those mutations, which meant that the response rates to any of these targeted drugs would not be particularly high. Therefore, we had to move on and consider immunotherapy first. As part of the whole immunotherapy thing, what happened was we in our phase 1 clinical trials program, where we develop new cancer drugs and do the first clinical trials of new agents, we had what we call an anti-pd-l1 antibody. About two years ago we didn t We sometimes have patients who have exhausted all conventional chemotherapy and there was nothing left, but my colleague, Dr. Renato Martins put a patient on trial and they had a complete response to this immunotherapy drug. And I had actually put a patient on that trial was not in the best of shape to begin with, but after a few treatments had actually gone from being so tired that he could barely do anything to going back to working full time. And he had almost a complete response in all the cancer that he had, so at which point we started being a lot more interested in putting patients on this. When we talk about immunotherapy, this is a new agent where a lot of the time your body should be able to recognize when there s a cell there such as a cancer. 4

5 We re [the body is]making mistakes all the time in terms of replicating, and when those mistakes aren t caught by your immune system they propagate and change into a cancer. So a normal person s body should be able to recognize that. Unfortunately, when you express a protein called PD-1 or PD-L1, which is the ligand on a tumor cell or some of these immune cells, it turns down the body s own immune system to be able recognize these cancers and destroy them. Immune System Okay. Let me just go over that to make sure we all understand. So your immune system--i always think of it like the bug zapper if we lived back east and had a lot of mosquitos or something--that bug zapper is there to zap these harmful cells in this case, or just ineffective cells that will just clog everything up, to zap them. And what you re saying is that these cancer cells express or put out sort of a chemical in a way that fools the immune system and says don t pay attention to me, leave me alone. Just go to sleep, forget I m here. Is that kind of right? Yeah, it s kind of like a marker, or it s a little protein that they express on top of the cells. So what happens is the cancer stimulates this protein expression on the cell so it can evade the immune system. Mm-hmm. They re like stealthy in a way. Mm-hmm. All right. So is the trial a way to get rid of that and have your own immune system go do its job? So the trial compound is an antibody or a protein that actually blocks this little target, this anti-pd-l1. Okay. And so then it sort of--am I right, it sort of reinvigorates the immune system, says, like a bloodhound, go get them? Yes, exactly. So it s saying look, now the cancer cells are no longer masked, and the immune system can say, look I can recognize you as a cancer cell. I can go out and destroy you now. Yeah. I always think, is it Star Trek or one of those where you take the cloaking 5

6 device or shield off the space ship and there it is, there s the bad guy, and you can destroy it. Okay. So, then you offered this to Eva. IV Therapy So this trial had been running for some time but the spots in terms of availability were running out, and it was only when patients aren t on chemotherapy that we could offer this. It seemed to be the last spot had come up when Eva was nearing the end of her chemotherapy, and we were able to grab it, secure it--i think around 40 patients were on there--and she was the last person who was enrolled. So, Eva, you ve been getting over many months now this IV therapy of this immunotherapy, right? Yes, I started October 14th of How has it been going? How are you feeling? I feel like a normal person. Really? I cannot report any side effects. And you re biking? I bike everywhere. I mean, I commute and I go everywhere on a bicycle. Okay. Do you feel like someone is sitting on your chest anymore? No. Can you bike up those hills? Oh, yes. 6

7 That s incredible. Not just bike up the hills but be actually competitive on the hills. Wow. You mean so if I m on a bike you re going to like blow me away, you re going to-- Pretty much. Oh, my. She d probably beat me, let s put it that way. So, Dr. Chow, what s going on? This sounds like a really big deal for the immune system--the obstacles are taken away so it can do its job in non-small cell lung cancer. So this is the first time we ve ever seen this in non-small cell lung cancer. I mean, traditionally we haven t found it to be one of the more sensitive treatments to chemotherapy, and once people exhaust chemotherapy we re really stuck dealing-- like there s nothing left to offer people, and this has been one of the biggest breakthroughs because we never knew that lung cancer could respond to manipulations in the immune system or that one cancer can be killed by regulating the immune system. So this is probably one of the biggest breakthroughs we ve ever seen in lung cancer treatment. Now, just looking at this more globally in lung cancer therapy, if we can get the immune system to do its job, wouldn t that be the best of all worlds? The immune system has helped us get over colds and fight infections and do so many things as we ve gone through life-- Wouldn t that be the most powerful medicine of all if we could help it do its job? Oh, for sure. And, the people that we ve treated have done well. We kind of think it s almost too good to be true. It s pretty amazing. The only tiny thing is it s not appropriate for people who have already hyperactive immune systems such as, having autoimmune disease or rheumatoid arthritis or other things like that --those are situations where people have already overactive immune systems, and we don t 7

8 necessarily want to make that worse. Treatment Approaches All right. Let me just see where this fits in now in what you re doing in non-small cell lung cancer. So obviously if lung cancer is found very early surgery remains the curative approach, correct? Yes. Okay. So if it is spread or more advanced, then we start talking about some sort of systemic therapy. Yes. So if I ve got it right, first you try to see is there a genetic mutation where you have a medicine for that? Well, so if it s in the early stages and if it s surgically removable we try and do surgery, and people can be cured with surgery. If they have some spread to the lymph nodes they may get some extra chemotherapy to decrease the risk of the cancer coming back. Sometimes when there s a lot of spread to the lymph nodes and the chest we try and cure patients with chemotherapy and radiation. Only in the situation when the cancer has caused a large amount of fluid in the lining or spread to the lining, that s not a situation that we can cure with surgery, chemotherapy or radiation. And when the cancer spreads outside the chest that s also not a curable situation, so we treat that--we try and give people medications to try and live longer and try to improve their quality of life, and usually those would involve either medications you take by mouth or intravenously. Okay. And that s why those genetically targeted medicines can come into play? Yes. So traditionally chemotherapy has been the role that has been playing until probably about two years ago where we realized that genetic mutations can predict who would respond to just the pill. So if you have one of these genetic mutations, either EGFR or ALK now we re looking at some of the other mutations such as RoF- 1, we can predict whether we ll get a response to just the pill, and the response rates are quite dramatic. They can range from 60 to 70 percent, which is much 8

9 better to be taking a pill and have good response to treatment for a very long time, even up to years, versus having to do chemotherapy which has side effects. And chemotherapy response rates are somewhat in the 30s, which are not that high. All right. So we mentioned those inhibitors, EGFR, ALK, and we talked about others, and now we have this, ongoing trials related to the PD-1 and PD-L1. So where does that come into play, this last group, which I know made big news at your most recent big cancer meeting, ASCO, American Society of Clinical Oncology Where does that fit in with these pills, or do we know? We don t know. In fact we re actually doing some studies to look at that as well. The anti-pd-l1 trial is near completion in terms of the lung cancer arm. I think we have one or two spots in terms before the lung cancer arm is completely filled, and we will be looking and analyzing the final results in the upcoming few months to upcoming years. In terms of other studies that we ve brought in, the anti-pd-1, which is the one that they re putting forward and has had all the press in the publications, in The New England Journal as well as The New York Times, that s being run right now as a first-line trial that we have open of which I m the primary investigator. What we re doing is adding this anti-pd-1 in patients that get diagnosed with lung cancer previously untreated. So what we re doing is adding this in with chemotherapy, and we re also adding it in for people that have an EGFR mutation that have been on Tarceva. As sometimes Tarceva doesn t work forever it s a very good opportunity to see if we can improve the response to Tarceva. We re adding in with Avastin, or bevacizumab, which is an antiangiogenic agent as maintenance therapy after chemotherapy as well as giving it for the first time first line instead of chemotherapy. Wow. So let s put this in the context of the discussions you have with people now at the Seattle Cancer Care Alliance, you being a drug development researcher in this field. So it sounds like when somebody comes in now with non-small cell lung cancer, depending upon their specific situations, you have a few options to talk about. A lot of it is in research, you don t always have the answers, but you have things to talk about, when if we go back just a few years you didn t. Yeah, it s pretty impressive actually that we re now able to offer people as another line of therapy something that has minimal side effects and can actually make them live longer and live better. And I actually think it s going to probably take over as being better than that of chemotherapy. Researchers are still trying to look at trying to determine what is it that makes some people respond to this better than others, and we re still working that out and it hasn t been fully established, but we re seeing if there is a marker on the cell that we can actually look at. 9

10 As part of the whole clinical trials portfolio, the current trial that we re running right now can only put on a small number of patients-- so all day today we have been trying to get some of our patients onto the study that just opened. But we will be starting off a very large phase III trial, enrolling several hundred people on either conventional chemotherapy versus the anti-pd-1 in the second-line setting. So there will be two trials doing that, and I believe sometime in August we re doing a combination of the anti-pd-1 plus another immunotherapy and also of tumors in an extended arm in lung cancer. So we have a large number of these trials coming up. Wow. Wow. Wow. That s what s so exciting about what you re doing at the Seattle Cancer Care Alliance. Now, let me talk about that. So somebody is listening to this, and they say, well, you just mentioned that they re comparing chemotherapy with, I don t remember if it was anti-pd-1 or PD-1, but at any rate, and they say, I want to get this in on what may be really exciting. If I don t respond to chemotherapy, do I have a chance to be in that arm? How does that work? So the big trial that will be coming up will allow anti-pd-1 versus chemotherapy, so unfortunately they won t necessarily have a choice. The current study we have rolling right now is in the first-line setting, and it s a phase I trial. Although we know a lot about the anti-pd-1, we don t know exactly what kind of side effects we will have when we combine it with either targeted therapies or chemotherapy, and that would be the experimental part of it. However, we re very optimistic that there s been several hundred people already tested on the anti-pd-1 and the anti-pd-l1 program, and we ve actually been running most of these trials here so we do have a fairly good experience in terms of how to manage these side effects. Probably the most important thing is it offers ourselves, physicians, a lot more hope, and we feel a lot more optimistic that there is indeed something that can be quite miraculous and help people and make them live longer in addition to just chemotherapy and targeted treatments. Clinical Trials Wow. Well, this is a very upbeat discussion, but let s hear it from Eva s point of view. How do you feel? I mean, nobody wants a diagnosis of, well, any cancer-- I m a leukemia survivor-- but certainly not lung cancer. I know they probably had to pick you up off the floor when you were told that. It s a very scary diagnosis. So for you now with the timing of receiving this medicine right as it s being tried and it seems to be having positive effect, this is almost sort of a blessing, isn t it? I mean, it s a bad diagnosis, but the timing of your illness with this, what appears to be medical progress is a good thing, isn t it, Eva? 10

11 Well, I guess it s being in the right place at the right time and meeting somebody at the Seattle Cancer Care Alliance who is passionate about clinical research and not afraid to put people in there, and I just feel fortunate to meet Dr. Chow. Right. Right. Let s talk about this for a minute. So there are people listening and they say, clinical trials, I don t know. It s like a lab experiment. I don t know if I want to be a part of it. And I should tell you I ve been in two trials, and certainly I would not be alive today having not been in a trial, so I m a big fan. But what would you say, Eva, for our listeners to at least consider it? I think I have to say what I have--i pondered over this. It s not an easy decision to make since nobody knows what it is, but I guess in my perspective I had nothing to lose but everything to gain. I figured if this doesn t work, worst-case scenario I ll just go back to traditional chemo and plod along a little while longer. Knowing what the statistics are and knowing what that would mean for my body, I decided to give it a try with the encouragement of Dr. Chow and her team. So you continued to receive medicine and you feel good. You got your three daughters. So how do you think about the future or even every day now? I don t. It s one cycle at a time, one cycle being six weeks, which then I have to have a CT scan and the verdict of the CT scan. And then you breathe again for six weeks and then the cycle continues. Hmm. But let s go back to when you first got that diagnosis, the first doctor you spoke to. I mean, it was out of that discussion you were calling your lawyer and putting your affairs in order, right? Yep, pretty much. That was the first phone call I made. Hmm. That s still--i m a very pragmatic person, as Dr. Chow would probably tell you. I was not on the floor. I did not have to be scraped off the floor by anyone. I thought about it. I did what I had to do, and I prepare for the worst every time and hope for the best. That is basically how I approach this. Right. But, Dr. Chow, you used the word hope earlier for, as you say, for 11

12 physicians who specialize in this field. I get the sense, knowing we re dealing with very serious illness, that still there s some excitement in the research community about having the immune system be reactivated, if you will, with such positive effect. We re very excited. I think this was probably one of the most exciting and leading talks when it was presented at the American Society of Clinical Oncology, which is the international meeting just last few weeks ago. It probably was the highlight of the whole conference. I think we at the Fred Hutch here and the Seattle Cancer Care Alliance knew about this, but we couldn t really say anything, and having the rest of the world find out about this has been really exciting. So I think we re hopeful, but as a drug developer we re always hopeful that we can find something that works better for our patients and can do better than what s out there. Personalized Medicine One of the things I get from this, though, is this thing we ve been talking about, this concept we ve been talking about for I guess a couple of years now, is personalized medicine. Mm-hmm. And that is how if you can have expanding drugs available in trials or approved therapies what approach--not just drugs, but we talk about surgery and radiation as well--what modality lines up with your specific case, if you will, and that s increasingly true, isn t it, Dr. Chow? I think it s great because we do have the ability to spare people the side effects of treatments that don t work for them and be able to select the people that can have treatments that work amazingly well for them. I m not sure where immunotherapy is going to lie in terms of this because we don t necessarily have a perfect marker for immunotherapy yet, but I do think it s been a lot more hopeful, and it really has allowed us to treat patients better. But, on the other hand, when patients come and talk to their doctor it always is a personalized thing where we try and choose the best possible treatment for our patients and have a discussion regarding the pros and cons of each one. And that is so important I think for people to understand. All the answers are not known now. And as you heard from Dr. Chow, this is a very solid example of progress. And Eva biking up the hill and going to work every day and being with her daughters, that s very a solid example as well. But there s still a lot to find out. 12

13 All I can say to you, Dr. Chow, is go for it. I hop there are many opportunities for people to participate, you get the answers, and when you go to the ASCO meeting or other big national and international meetings there are other big, exciting talks, and the doctors look at the research and patients being helped and you just say wow. I wish that for you. Well, thank you so much. And I myself feel very fortunate, actually, to be here. I ve only been here for the last two and a half years. I came from Canada, and having the resources of Fred Hutch as well the CITN, which is a huge immunotherapy network, and all these great researchers here have really made it a pretty incredible place to work. And one other point I was going to ask you to make is you are very thankful for the patients who participate in the trials, aren t you? Oh, for sure. I mean, these patients actually led us into the light. They actually go onto these trials, and they provide information that s so important for the future, and any of the breakthroughs that ever come out is from our participation from our patients. Closing Thoughts Well, Eva, I know you didn t want to see yourself being a pioneer or a pathfinder in this regard, you d rather be winning the bike race, but I just want to thank you for your participation in this. I m glad it s benefitting you personally, but the information that comes out of it can help so many people to follow as well. And, Eva, any final comment you wanted to make, how you re feeling? I just wanted to say this is definitely a second lease on life for me. Maybe it s not going to last too long, but the quality of my life is basically the same if not better than what it was before diagnosis, and any other therapy I don t think would have been that good. So I think for me, that s the most important, that I live like a normal person, look like a normal person, and most certainly act like a normal person. Well-- At least according to me. 13

14 Well, to me, you re an extraordinary person, and I want to thank you for being with us, Eva Borsi. I wish you well in your daily activities for sure, and when I see that bike flash past with a woman on it I m going to know that s you, okay? You re going to know because it s pink, so. Oh, pink. Yes. Okay. It s a pink, single-speed bicycle, so you can recognize it anywhere. Going a thousand miles an hour uphill. Yes. Okay. All right. Eva Borsi, thank you so much for being with us. Thank you. And Dr. Laura Chow from the Seattle Cancer Care Alliance and Fred Hutchinson Cancer Research Center, thank you for all you do, and thank you for being a team with your patient Eva. I know she s very thankful. Yes, yes I am. Okay. Thank you, Dr. Chow. Thank you. All right. This is really a positive story in cancer and we re delighted to bring this to you but with a lot more information to come, a lot more questions to be answered. 14

15 After all, we re talking about research, but it s still a very positive story. I m Andrew Schorr. Thank you for joining us. Remember, knowledge can be the best medicine of all. Please remember the opinions expressed on Patient Power are not necessarily the views of Seattle Cancer Care Alliance, its medical staff or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That s how you ll get care that s most appropriate for you. 15