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Beating Cancer With Immunotherapy
1
Three patients who have treated cancer with immunotherapy discuss their experiences.
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Crispin: Hi. My name is Crispin. I was diagnosed with cancer in 2015.
Michael: I'm Michael. I was diagnosed with cancer.
Leta: I was first diagnosed in May of 2013. They determined it was melanoma.
Crispin: I had these odd, crippling chest pains that went on for months on end, like, out of nowhere, I'd have what I thought was a heart attack. I went to go see doctors thinking it was some kind of heart problem or pulmonary problem.
Michael: He came out after I had woken up, and he sat down next to me. I kept thinking, doctors don't sit down next to you. This isn't boding well.
Crispin: I went through tons of tests, only to realize there were actually, in fact, tumors inside of my chest. It was metastatic melanoma, which is somewhere between a late stage 3, early stage 4 metastasized melanoma.
Michael: You really didn't need to be a physician to recognize the ulcerated tumor as being cancerous.
Leta: Take a step back and take a deep breath. Give it some space, because it's so terrifying, and it's so easy to rush in to treatment.
Crispin: For two days, I was sad and I cried more than I will probably cry in my life combined moving forward. I was more angry than anything. I let that anger drive me.
Leta: The first treatment option that I was given was surgery to remove the large tumor.
Crispin: Two was chemo, and obviously the rates that they give you for chemo survival of this kind of thing are scary.
Michael: Unfortunately for myself after five treatments, I was really starting to wonder what was going to kill me first: was it going to be the cancer, or was it going to be the chemotherapy?
Crispin: And then three was the trial.
Michael: He presented this possibility of something called immunotherapy.
Crispin: I got my first infusion of the immunotherapies. I walked out of the hospital that night and I felt totally normal.
Michael: The trial was a year long, so it was every other week. I would go down and have an infusion.
Crispin: After a while, though, I was warned of this up front: the immunotherapies don't know if they're attacking good or bad things. You just hope they're attacking the bad things with the good. After two infusions, my liver got so bad, they pulled me off of infusion number three and number four. But they still scanned me, and the results were pretty strong, even with just two infusions.
Michael: The best part of it was that after three months, they weren't finding the cancer any longer that had been in my liver.
Crispin: He told me in my last checkup in November that I'm probably going to be able to live a normal life.
Leta: I have had clean scans for almost three years now.
Crispin: Part of it's just knowing what is out there, because you think chemo the minute you hear cancer. And it's not that anymore for a lot of advanced diseases.
Leta: The most important thing that I learned was that it's okay to also ask for help. Knowing that all those people were rooting for me and my family made a world of difference.
Crispin: Get on the phone. Call somebody who might know something more than you do.
Michael: Be an advocate for yourself. Don't just necessarily sit back and let the doctor lead you from one thing to the next, but be aware of what they're doing and why they're doing it.
Crispin: Everyone says it, it's kind of cliché, but just keep living your life however you can.
Michael: One of the things I want to give people is a little bit of hope. Don't immediately think the worst. Try to be optimistic about it.
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Beating Cancer With Immunotherapy
1
Three patients who have treated cancer with immunotherapy discuss their experiences.
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Crispin: Hi. My name is Crispin. I was diagnosed with cancer in 2015.
Michael: I'm Michael. I was diagnosed with cancer.
Leta: I was first diagnosed in May of 2013. They determined it was melanoma.
Crispin: I had these odd, crippling chest pains that went on for months on end, like, out of nowhere, I'd have what I thought was a heart attack. I went to go see doctors thinking it was some kind of heart problem or pulmonary problem.
Michael: He came out after I had woken up, and he sat down next to me. I kept thinking, doctors don't sit down next to you. This isn't boding well.
Crispin: I went through tons of tests, only to realize there were actually, in fact, tumors inside of my chest. It was metastatic melanoma, which is somewhere between a late stage 3, early stage 4 metastasized melanoma.
Michael: You really didn't need to be a physician to recognize the ulcerated tumor as being cancerous.
Leta: Take a step back and take a deep breath. Give it some space, because it's so terrifying, and it's so easy to rush in to treatment.
Crispin: For two days, I was sad and I cried more than I will probably cry in my life combined moving forward. I was more angry than anything. I let that anger drive me.
Leta: The first treatment option that I was given was surgery to remove the large tumor.
Crispin: Two was chemo, and obviously the rates that they give you for chemo survival of this kind of thing are scary.
Michael: Unfortunately for myself after five treatments, I was really starting to wonder what was going to kill me first: was it going to be the cancer, or was it going to be the chemotherapy?
Crispin: And then three was the trial.
Michael: He presented this possibility of something called immunotherapy.
Crispin: I got my first infusion of the immunotherapies. I walked out of the hospital that night and I felt totally normal.
Michael: The trial was a year long, so it was every other week. I would go down and have an infusion.
Crispin: After a while, though, I was warned of this up front: the immunotherapies don't know if they're attacking good or bad things. You just hope they're attacking the bad things with the good. After two infusions, my liver got so bad, they pulled me off of infusion number three and number four. But they still scanned me, and the results were pretty strong, even with just two infusions.
Michael: The best part of it was that after three months, they weren't finding the cancer any longer that had been in my liver.
Crispin: He told me in my last checkup in November that I'm probably going to be able to live a normal life.
Leta: I have had clean scans for almost three years now.
Crispin: Part of it's just knowing what is out there, because you think chemo the minute you hear cancer. And it's not that anymore for a lot of advanced diseases.
Leta: The most important thing that I learned was that it's okay to also ask for help. Knowing that all those people were rooting for me and my family made a world of difference.
Crispin: Get on the phone. Call somebody who might know something more than you do.
Michael: Be an advocate for yourself. Don't just necessarily sit back and let the doctor lead you from one thing to the next, but be aware of what they're doing and why they're doing it.
Crispin: Everyone says it, it's kind of cliché, but just keep living your life however you can.
Michael: One of the things I want to give people is a little bit of hope. Don't immediately think the worst. Try to be optimistic about it.
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Benefits of Immunotherapy
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With certain cancer patients, immunotherapy can give people the chance to have a normal life.
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Dr. Sacher: The most positive thing about immunotherapy is that, in a subset of patients, it can really give them back the chance to have a durable response and a normal life.
Dr. Arena: If I were to take someone who had advanced lung cancer, and I would use the best chemotherapies that I could have, the numbers are monotonously the same - a response rate that is only about 23 to 26%. I could use immunotherapy, and I will get a response rate of over 40%. That is a totally new game.
Dr. Subramaniam: The quality of life in a patient treated with immunotherapy is much better than the quality of life while on chemotherapy.
Dr. Sacher: And in fact, many patients will go on to have no real significant side effects from the treatment at all.
Michael: I didn't have any kind of pains. I didn't have muscle aches, joint aches. I was back to normal.
Crispin: I got my first infusion of the immunotherapies and I walked out of the hospital that night and I felt totally normal.
Dr. Arena: And most importantly, now I have responses that can last a long, long time.
Dr. Subramaniam: In a patient with newly diagnosed lung cancer, who starts on chemotherapy, the benefit lasts for anywhere from seven to nine months, and some chemotherapy drugs, possibly 10 months.
Dr. Subramaniam: However, with immunotherapy, the response frequently lasts greater than a year.
Dr. Sacher: I think that's something that we never really saw before in metastatic disease. And I think that is the really extraordinary thing about immunotherapy. Going forward, we really want to try to develop newer immunotherapies that can bring that benefit to more patients, in order to allow them to derive that benefit and hopefully avoid treatments that have worse toxicity profiles.
Dr. Arena: I want both quantity and quality. Never one without the other. And if I can give a therapy that's much more resilient, much more able to be tolerated, and it works better, it doubles the response rates, it makes people have a progression-free survival much, much longer, wow. That's the new era.
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Is Immunotherapy Right For You?
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Immunotherapy doesn't work for all patients with cancer. Who is it best for?
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Dr. Arena: When a patient comes to see me and says, "Doctor, am I a candidate for immunotherapy?" And the first thing is, I wanna know what disease we're talking about.
Dr. Subramaniam: Immunotherapy does not work for all patients with cancer.
Dr. Sacher: Questions that I wish patients would ask more is, "Is immunotherapy right for me and right for my disease at this time?"
Dr. Markman: One of the very important factors that appears to be relevant is the presence of certain biomarkers within the cancer itself.
Dr. Subramaniam: That will give us a clue as to whether immunotherapy will be effective in that patient or not.
Dr. Markman: They don't prove that therapy's going to work, but they predict that a therapy, one of these therapies, will work.
Dr. Sacher: In patients whose tumors express high levels of this protein, called PD-L1, the effectiveness of immunotherapy is much higher than in patients whose tumors do not express high levels of that protein. Patients whose tumor expresses lower levels might benefit actually from more standard treatments to start, reserving immunotherapy for later on in their treatment.
Dr. Arena: For the most part, it's given once every three weeks intravenously. Takes about 30 to 40 minutes.
Dr. Sacher: Because immunotherapy works by waking up your body's immune system to help it attack cancer cells, you can sometimes see that those immune cells may occasionally misfire and attack normal tissues. In the rare patient where that happens, it produces what's known as an immune-related adverse event.
Dr. Markman: There can be diarrhea. There are cases of people who have developed diabetes.
Dr. Arena: But here's the deal. We can treat that. We can give the patient steroids.
Dr. Markman: That quality of your life is defined by a variety of parameters and that's critically important, but equally important to the kinds of quality of life, is who defines it and it's the patient. Period.
Dr. Arena: What's so important here is that the toxicity profile is number 1, totally different than chemotherapy. And number 2, that the idea that most patients will get very little, if any, of these toxicities is amazing. Immunotherapy, as we see at this moment, is not for everybody but that's okay. We're moving towards getting more and more people into that quandary of what can be done for them immunotherapy-wise.
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My Experience With Immunotherapy
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Leta talks about her journey with advanced melanoma, from discovery to diagnosis to treatment with immunotherapy.
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I was first diagnosed in May of 2013. They determined it was melanoma. I noticed that I had a big, lumpy bruise on the back of my leg. They did an MRI, and they initially weren't sure what kind of mass it was. But once they did surgery to remove it and did pathology on it, they determined it was melanoma. They knew that it had already metastasized. It metastasized to my small intestines and my lungs.
The conversation with myself was to really not get my hopes up, based on the prognosis and everything that I'd seen and read about stage 4 melanoma. The prospect didn't look very good for long-term survival. My brother had actually been diagnosed with leukemia, I don't know, three or four weeks before my diagnosis. My family was pretty overwhelmed with that, so I actually kept the news to myself for a few weeks. I found an article about some new immunotherapy options online, and that took me to a search for clinical trials.
Dr. Atkins explained that I would get infusions of two different immunotherapy drugs. They happened, in the beginning, in two week intervals and then moved to three week intervals. The first scan was, I believe, six to eight weeks after the first treatment. The tumors were already shrinking at that point. When I started seeing good results, it almost felt a little foolish to believe them. The more good results I got, the easier it was to start sort of relaxing into that sense of hope that I would actually get better. Sometimes you're supposed to have a brave face, and you're not always going to have a brave face, and that's okay, too.
I mean, I certainly had a will that I wanted to live and to thrive. I'm married and I have two daughters, and I couldn't imagine them growing up without me. I wanted to be there for my family. I have had clean scans for almost three years now. I'm back teaching. I teach four year olds. They're very active, so I have to be pretty active too, but overall, you know, things are pretty great.
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What Is Immunotherapy?
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What is immunotherapy, and how can it fight cancer? These experts explain this exciting new treatment.
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Dr. Arena: What immunotherapy is doing is unleashing the dogs.
Dr. Sacher: Immunotherapy works by helping your body's own immune system recognize and attack cancer cells.
Dr. Arena: It's allowing your own body to take charge.
Dr. Sacher: Your body's own immune system, as part of its natural function, recognizes abnormal cells and attempts to get rid of them. In a patient that has cancer, we frequently would see that their own immune cells were standing by and not really attacking cancer cells, even though cancer cells are the most abnormal cells you could find in someone's body. That, for a long time, really puzzled oncologists.
Dr. Markman: Why is it that these cells are not helping to kill the cancer? They're there, but they're not doing anything. Well, perhaps it's not that the immune system isn't ready to go. It's not that the cells aren't there, but somehow they're blocked from working.
Dr. Sacher: PD-L1 is a protein that is normally expressed on your body's cells in order to reduce inflammation, essentially a signal that your body's normal cells can use in order to say, "I'm a normal cell. Don't attack me." Cancer cells can co-opt that mechanism by expressing extremely high levels of that protein.
Dr. Arena: And what it does is that these ligands will attach onto the activated killer T-cell as if it was a lock-and-key mechanism and turns off the motor. It stuns them.
Dr. Sacher: Essentially, taking a normal mechanism that your body uses to regulate inflammation and use it as a shield against an anti-tumor immune response.
Dr. Markman: The observation led to the development of a group of very exciting drugs known as checkpoint inhibitors.
Dr. Arena: It almost sounds like something out of "Star Wars." It blocks that PD-L1 and PD-L2 from attaching into the activated T-cell, almost like sealing wax that would go over the key holder, let's say in your ignition of your car, so that your key could not get into that ignition key holder.
Dr. Sacher: And allowing your body's own white blood cells to recognize, attack and ideally, eliminate cancer cells. So, they really serve to unmask a tumor and allow your body's immune cells to recognize it.
Dr. Arena: It's saying, "Hey, listen. We have a foreign body in our system. We are going to be on the attack." Immunotherapy is much more subtle. It's allowing your own body to take charge. That is a totally new game. That is bringing everything into overtime.
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Immunotherapy and Lung Cancer
44
Immunotherapy can offer a durable, long-term response to therapy for patients with lung cancer.
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Dr. Arena: If we talk about the effectiveness of immunotherapy in lung cancer, you have to know a little bit about where are we now, or where were we?
Dr. Sacher: Immunotherapy is the first class of agents that I've seen within lung cancer that really offer the promise of a durable, long-term response to therapy in patients with metastatic disease.
Dr. Subramaniam: There are two major types of lung cancer.
Dr. Arena: One is called small cell cancer of the lung, which occupies about 15% of all lung cancers ...
Dr. Sacher: ... and tends to be more heavily associated with smoking.
Dr. Arena: And then there's non-small cell cancer of the lung.
Dr. Subramaniam: And that may or may not be associated with smoking.
Dr. Sacher: Small cell cancer tends to grow very quickly and very explosively, but also is very sensitive to traditional treatments like chemotherapy and radiation treatment. Non-small cell lung cancer also responds to those treatments, but perhaps is not as sensitive.
Dr. Arena: The vast majority of cases of non-small cell cancer of the lung are what we call adenocarcinomas of the lung. Adenocarcinomas of the lung, there are about four or five different mutations which are so very important, because we have medicines, actually pills, that can be used for these specific mutations. The other most common is something called squamous cell cancer of the lung. We have multiple mutations in squamous cell cancers, and we don't have any medicines for them. So when I see a patient with non-small cell cancer of the lung, the first thing I want to know, is this a squamous cell cancer? Is this an adenocarcinoma of the lung?
Dr. Sacher: Lung cancer is an extremely aggressive malignancy. And for the majority of patients, it's diagnosed at a late stage.
Dr. Arena: And there are really no screening types of tests that one can do that really can make this an early diagnosis.
Dr. Sacher: The use of immunotherapy in lung cancer really is defined by specific biomarkers. What a biomarker is, is just a test that we perform either on a patient's tumor or sometimes on their blood in order to determine what treatment will be most effective for them.
Dr. Subramaniam: Markers in the tumors of patients that will give us a clue as to whether immunotherapy will be effective in that patient or not.
Dr. Sacher: We discovered that the expression of a protein called PD-L1 on the surface of tumor cells helps us to identify patients whose cancers are likely to respond to immunotherapy.
Dr. Arena: So I'm going to ask the pathologist, "Can you measure, on that cancer cell, the PD-L1?" And they can, within a few days, come back, "Yes, this tumor has got tons of that."
Dr. Sacher: Patients whose tumors express that high level are the exact patients who should be treated first with immunotherapy as opposed to starting with chemotherapy. I think it's important for patients to be cognizant of this because the testing for that biomarker really is so key to directing their care, which sometimes is immunotherapy, but sometimes it's not. The most positive thing about immunotherapy is that, in a subset of patients, it can really give them back a chance to have a durable response and a normal life. And that remission from their cancer can actually last years in the best-case scenario.
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Moving Beyond Chemotherapy
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Newer cancer treatments target specific mutations and stop cancers from advancing.
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Dr. Sabari: When I started treating patients, we initially started treatments with chemotherapy alone. There were really no other great options.
Dr. Rohs: The changes that we've made in the treatment and the advances we've had, even in the past year or two, are amazing. The treatments are much more effective and more durable, as well as more tolerable.
Dr. Lackey: The classic chemotherapy that people think of when they hear the term chemotherapy, doctors call that cytotoxic therapy. Cytotoxic means toxic to cells. Not just cancer cells, but all the cells in the body.
Dr. Liaw: The tough thing with traditional chemotherapy is that, because it can affect both cancer cells as well as normal cells, that we do have a lot of potential issues with side effects.
Dr. Lackey: But in this day and age, it's very exciting because we have additional therapies we can offer patients.
Dr. Kazmi: Targeted therapies attack cancer at the level of the mutation. So, what turns a cancer on to grow and spread is usually a mutation or two or three. There are certain drugs that target those specific mutations that turn that on button on and stop it.
Dr. Liaw: Targeted therapy's really revolutionized how we treat things like lung cancer, colorectal cancer, some skin cancers, without causing quite as much of the side effects that we traditionally ascribe to a classic chemotherapy.
Dr. Rohs: Targeted therapies only work for patients with these genetic mutations. I wish we could be able to give this to everybody, but we have to make sure we're giving it to the right patient at the right time.
Dr. Lackey: Now, the newest evolution of therapy is what's called immunotherapy.
Dr. Sabari: Normally, our immune system is able to recognize and attack things that are foreign. Interestingly, cancer is able to fool the immune system to prevent it from recognizing it. With immunotherapy, we're able to remove the brakes from the immune system to then allow the immune system to better recognize and attack the cancer.
Dr. Kazmi: Immunotherapy has the benefit over chemotherapy in that it doesn't give you the nausea, the vomiting, the hair loss; however, immunotherapy can have different side effects.
Dr. Sabari: What we do worry about most is if we actually rev up the immune system to an extent where it can recognize and attack your own body, we worry about auto-immune or inflammatory conditions. But these side effects are rare, and actually, very well tolerated and they're very well treated.
Dr. Kazmi: There are also new studies that show us that a combination of immunotherapy medicines with chemotherapy has a significant amount of synergy. There's also immunotherapy medications combined together with different types of immunotherapy to increase that synergy.
Dr. Liaw: I think it's still a little bit too early for us to say that chemotherapy will be entirely phased out. If things like targeted therapy is, for whatever reason, not that effective, or if things like immunotherapy are not giving us the desired results, it's still important for us to have things like chemotherapy in our back pocket to be able to use when necessary.
Dr. Sabari: I think over the next five to 10 years, we'll start to see more and more combinations of therapies, and I do hope that in my career, in my lifetime, we do see this disease cured.
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Treating Advanced Lung Cancer
16
If lung cancer is advanced, sometimes surgery isn't enough. Learn from these experts how they treat advanced lung cancer.
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Dr. Subari: There are two major subtypes of lung cancer. The most common one is non-small cell lung cancer, and the second type of lung cancer that we see is a lot less common and is a more aggressive subtype called small cell lung cancer.
Dr. G: We don't do surgery for small cell lung cancer. Usually, it's a combination of chemotherapy and radiation.
Dr. Kazmi: Non-small cell lung cancer, if the cancer is early stage, surgery is the mainstay of the therapy. If, however, it's more advanced, sometimes surgery is not enough. When a cancer is metastatic, patients need systemic treatments, such as chemotherapy, immunotherapy, or targeted therapy.
Dr. G: Targeted therapy is based on the idea that there are specific gene mutations that drive a person's cancer. If we can figure out what those gene drivers are for that particular patient's cancer, we can then find a drug that can then target that gene mutation.
Dr. Rohs: One of the really nice things about these pills is that they are well-tolerated and they can get to disease that other treatments can't get to.
Dr. Subari: If we're not able to identify a genetic abnormality that we can match with a pill, we're then going to talk to you about chemotherapy and/or immunotherapy. The way that we decide which one to use depends on something called PD-L1 that sits on the surface of the cancer cell, and if you have a high level of this PD-L1, we generally recommend immunotherapy first, and if a person has a low level, we're going to recommend chemotherapy and immunotherapy as the first treatment option.
Dr. G: Chemotherapy is treatment basically that kills cancer cells, but it also kills the good cells.
Dr. Kazmi: Chemotherapy tends to work really well for certain cancers. However, it has side effects on the body in terms of the blood counts, the hair, the weakness, so it's not a long-term, sustainable plan.
Dr. Lackey: The newest evolution of therapy is what's called immunotherapy. Our immune system is probably the best tool we have to keep our bodies healthy. Question always was, why can't the person's immune system fight off the cancer?
Dr. Subari: Cancer is able to fool the immune system to prevent it from recognizing it. With immunotherapy, we're able to move the disguise, remove the brakes from the immune system, to then allow the immune system to better recognize and attack the cancer.
Dr. Kazmi: Immunotherapy comes in a variety of forms. The most common of these are called checkpoint inhibitors or PD-L1 inhibitors. They are the drugs that turn on the immune system and turn your T-cells on to go and attack cancer.
Dr. Rohs: Immune therapy, one of the most amazing parts of it is that it's very tolerable. Many patients don't have many side effects. Sometimes, they're a little bit more tired, their appetite can be down, and they can have something called immune phenomena. Because we're using your own immune system to attack the cancer, occasionally the immune system gets a little confused, and it can attack your own body.
Dr. Subari: I think this is an extremely exciting time in the treatment of people with lung cancers.
Dr. Kazmi: Immunotherapy has been a beacon of hope that cancer has needed for decades.
Dr. Rohs: The pace of discovery for lung cancer right now is so staggering. I think we really are coming into the era of personalized medicine where we can hopefully minimize treatments and maximize benefits for our patients and have them live longer and live better.
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