New Cancer Treatments – Immunotherapy and Targeted Therapy

Transcript of Episode 8: New Cancer Treatments
The Thing About Cancer podcast, Cancer Council NSW

[Series intro]
[woman] The very essence of all cancers is a change in the way that cells divide.
[music]
[man] I remember sitting in there thinking, you know, it’s not happening, it’s not real, it can’t be real.
[woman 2] It’s something that we don’t talk about.
[woman 3] This feeling of being overwhelmed − it will get better once you have a plan and you know what to expect and what’s going to happen. It’s not going to be like this all the time.
[various voices] The Thing About Cancer: A podcast from Cancer Council NSW. Information and insights for people affected by cancer.

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Julie McCrossin: Hello, I’m Julie McCrossin and today the thing about cancer is that new treatments are emerging all the time.

Steven Kao: Targeted therapy, five years ago that was the most exciting thing that was happening. The question today, what is the most exciting and important thing that’s happening in the cancer treatment area? I would say immunotherapy.

Julie: We’re talking to Dr Steven Kao, a medical oncologist from the Chris O’Brien Lifehouse in Sydney. You might have heard about immunotherapy and targeted therapy in the news, or perhaps your doctors have recommended them as part of your cancer treatment. But what exactly are they and how are they different from traditional chemotherapy?

In a moment Steven’s going to tell us all about these exciting new treatments. Just to be clear, this podcast contains general information only, so we recommend you talk to appropriate professionals about your individual situation. You can also call Cancer Council 13 11 20 if you have any questions.

To begin, there are three main types of treatment for cancer, can you run through just in a nutshell what each of them is and what they involve and then a little bit more on what you do as a medical oncologist, but what are the main three, to fit your work in with that other triad?

Steven: Yes, so I guess the first weapon that’s probably best known to our patients is surgery. So I guess to cure a cancer we really need to take it out if possible. The second weapon we have is radiotherapy and essentially that’s very high dose x-rays to target localised cancer spots, and so that’s what radiotherapy or a radiation oncologist would do. The third weapon really is what I call systemic therapy and that’s what I do − I’m a medical oncologist and that’s my job, to prescribe systemic therapy.

Julie: And what does that mean?

Steven: So systemic therapy essentially means it’s a treatment that gets into our patient’s body and circulates everywhere, whether it’s through a tablet which then subsequently get absorbed into the bloodstream, or you go directly into the bloodstream via intravenous infusion, so that it can target all the cancer spots in the body. And that can be divided into either chemotherapy, hormonal therapy, targeted therapy or immunotherapy.

Julie: Okay, so could you explain what chemotherapy is?

Steven: So chemotherapy is basically a drug that is designed to kill cancer cells. So that’s what we call cytotoxic.

Julie: Now that word cytotoxic, I understand that cyto means cells, so it means the drugs are toxic to cells?

Steven: Well essentially it typically affects the way the fast-growing cells divide and causes them to die.

Julie: Because cells dividing is how they grow, and cancer is like too much growth?

Steven: Correct, and that’s why chemotherapy is designed to target those fast-growing cells.

Julie: I think chemotherapy is the systemic treatment that most people have heard of, but you mentioned there are three other types of treatment that you as a medical oncologist might recommend. There’s hormonal therapy − I understand some cancers like some types of breast or prostate cancer grow in response to the body’s natural hormones, so hormonal therapy can be used to block those hormones and stop the cancer growing. And then there are the two newer types of treatment: targeted therapy and immunotherapy, and that’s mostly what we’re going to talk about in this episode. Can you give us an idea how common it is to get these newer treatments?

Steven: Well look, I think that’s a very difficult question to answer because I can’t generalise this for different kinds of cancers. Now you know, there are cancers like brain cancer that really has no specific targeted therapy of note currently, and then on the other hand you have lung cancer whereby we know about 20−25% of lung cancer patients can be potentially eligible for a targeted therapy. And so it’s really difficult to know what we are talking about in terms of the proportion of patients that are eligible for this type of targeted approach to their treatment. But certainly different cancers would have different kinds of targets, different kinds of treatment, and that needs to be discussed with their oncologist, and certainly it is not a treatment that would be suitable for everybody.

Julie: Okay well let’s talk about these new treatments in turn. First of all what is targeted therapy?

Steven: You know, some cancers have specific genetic changes that we believe are driving the cancer to grow, to divide and to spread. And so if we find a specific target then we can use a targeted therapy, again whether it’s oral tablet or intravenous infusions, basically the drug is targeting this specific genetic abnormality to stop it growing and dividing and spreading.

Julie: How is it different to chemotherapy?

Steven: Yeah, so I guess traditionally what we think the effect of chemotherapy is that it’s not targeted. Although it’s targeting fast-growing cells, there’s a lot of fast-growing cells in our body as well, such as hair, the lining of our gut, and that is why we get significant side effects with nausea, vomiting, the diarrhoea, the hair loss and things like that. So while it’s targeting the fast-growing cells, a lot of our normal cells get affected and that’s why the side-effect profile is so high. Now in terms of targeted therapy as I mentioned, we’re trying to find a genetic abnormality within the tumour cells, so that the idea is that the drug would target that abnormality to stop it from growing. So theoretically it sounds fantastic and you know theoretically the side effects would be substantially better than a blanket treatment that may affect all cells. So in terms of side effects it’s much, much better. It’s not side effect free, though it can still have side effects, just much more milder.

Julie: And are there some circumstances in which some side effects of targeted therapy can be more serious and of more concern? That while generally there’s lesser side effects, there are exceptions to that that it’s important to let your clinical team to know about if you experience them?

Steven: Oh absolutely. So I guess there’s potential severe side effects with any of the treatments that we prescribe. So, for example, you know Tarceva or Iressa is a targeted therapy for lung cancer. Now while we know from clinical trials it’s much better tolerated by chemotherapy, there are specific side effects that we warn our patients about, such as diarrhoea or rash. Now while rash often is a cosmetic concern for patients, it can be very annoying and distressing for patients, and certainly diarrhoea sometimes, really it can get so bad that we need to stop the drugs. And so while the chance of you having severe side effects is much better than chemotherapy, it’s not impossible, and people still need to be aware of the importance of recognising those problems.

Julie: So basically so you just keep talking to your team and letting them know what’s happening to you and is this normal?

Steven: Correct, correct.

Julie: Let’s turn now to immunotherapy, this exciting development in cancer treatment, can you explain what immunotherapy is?

Steven: That is a brand new kind of approach looking at trying to increase each individual’s immune system to try to recognise cancer cells. You know cancer cells are very smart little things, basically they develop mechanisms to protect themselves. Now our immune system is designed to detect anything that shouldn’t be there, so whether it’s an infection, a bug or cancer cells that shouldn’t be there, they basically should be recognising them and killing them. And somehow the cancer cells have become very smart, they evade the surveillance from the immune system and that’s how they keep growing. And so immunotherapy is a way to try to boost our immune system up so that they can start seeing those horrible little cells so that they can kill it.

Julie: I understand there are different types of immunotherapy but the older drugs weren’t that successful, what is this new immunotherapy that everyone’s talking about?

Steven: Checkpoint inhibitors, which is the most common immunotherapy that the oncologists are talking about really, and it’s got to do with a pathway in which we stimulate the immune system. Checkpoint inhibitors basically encompass Keytruda and Opdivo.

Julie: And can you explain Keytruda, is that for curative intent or for palliative intent? And is it used in particular cancers?

Steven: So I guess Keytruda or Opdivo at the moment, we are finding great results with melanoma in the palliative setting. There’s also increasing evidence that it’s effective in lung cancer as well. Now the landscape as you said is moving so fast, there’s lots of research and I suspect that it’s going to be coming on board for our head and neck cancer patients, you know bladder cancer patients and so I think that landscape is moving pretty quickly. Now there’s a lot of interest of bringing the immunotherapy in the curative intent setting, and that’s where a lot of research is being done. So people who have surgery followed by chemotherapy, and the question is whether adding immunotherapy to that for a certain period of time would increase the cure rates. So at the moment we’re not using immunotherapy in the early-stage cancers but it may change.

Julie: Steven, I understand you can still get side effects with immunotherapy. If we’re boosting the immune system, why should there be troublesome side effects? Surely if the immune system is working better it should be okay?

Steven: Yeah, so I guess if your immune system is too active, then potentially it can start gobbling up your normal cells. And again it’s expected potential side effects and we call that immune-related problems − or it resembles in the general population those autoimmune problems. So essentially it can cause inflammatory changes in any of our organs. So it can affect the skin, causing a rash, it can cause arthritis because it causes inflammation in the joints. But more seriously it can cause inflammation of your lung, it can cause inflammation of the liver, kidney, the intestine, causing life-threatening problems, because essentially your immune system is turning its head against your normal organs.

Julie: And presumably you monitor the patient closely to check these negative things are happening. How do you monitor?

Steven: Well so I guess there are things that we can objectively monitor, such as blood tests where we can see what the liver’s doing, what the kidney’s doing, we can see what the thyroid hormone’s doing because it can attack your thyroid gland as well. But a lot of it is also to do with educating our patients about symptoms because obviously we can’t objectively detect diarrhoea if there’s inflammation of the intestines, so we rely on patients to alert to us as well to the potential symptoms that can be indicative of something serious going on.

Julie: And the key symptoms to watch out for?

Steven: Well so there, as I said, there are multiple organs that can be affected, so there are multiple symptoms that can occur. So I guess if we’re talking about inflammation of the intestine, people need to watch out for diarrhoea, people need to watch out for bleeding from the back passage and tummy pains. If we are talking about inflammation of the lung, people need to be aware that they may get more short of breath, they may start to cough and have chest pains and just feeling difficulty in breathing. Now the other thing to really emphasise is that this sounds all very scary, but the chance of very severe side effects and reactions is extremely low, and most people have very little or no side effects from those treatments. And again, the key is to work with your treating doctor and your treating team, with the nurses and everybody else so that if you’re not sure, just call and let them know what’s happening to you.

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Julie: You’re listening to The Thing About Cancer, a podcast from Cancer Council NSW.

I’m Julie McCrossin and I’m talking to Dr Steven Kao a medical oncologist from the Chris O’Brien Lifehouse about two key developments in cancer treatment: targeted therapy and immunotherapy. This is a rapidly changing area, so talk to your treatment team to find out the latest, and of course, you can also call Cancer Council 13 11 20 if you have any questions. If you want more information about how targeted therapy and immunotherapy work visit our podcast page − just go to cancercouncil.com.au/podcasts and click through to this episode. You can also go to that page to find more podcasts.

In a moment Steven is going to talk about the benefits of these two new treatments and how you might be able to get access to them.

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Julie: Let’s chat about the practical stuff, exactly how targeted therapy and immunotherapy drugs are given. I believe some of these drugs are administered like chemotherapy through an intravenous drip − that’s known as an intravenous infusion. Can you explain what’s involved for someone who’s listening to this and it’s literally their first encounter, they’ve never been to a chemo ward?

Steven: Yeah, so it’s not as scary as people think. It’s actually, we try to make the environment as relaxed as possible. Essentially it’s just like any wards − there may be chairs or beds that people sit or lie on to receive the treatment. For intravenous infusion essentially the nurse will come along, find a vein, put a cannula in to access that vein and then the appropriate drug gets infused into that drip and once that’s all done, we take that drip out and patients go home. So it’s all administered on an outpatient basis, you don’t need to stay in hospital per se to receive any of those treatments.

Julie: Can targeted therapy sometimes be tablets that you take at home?

Steven: Correct, so again, for example, Tarceva or Iressa, you simply take one tablet, once a day at home and you come and see your oncologist every few weeks to just make sure that everything’s going smoothly. So quite a few of those targeted therapies are administered at home via tablet.

Julie: And is immunotherapy also sometimes given as tablets?

Steven: Right now all the immunotherapy treatment are all intravenous. So there’s no tablet form of immunotherapy drugs.

Julie: If you’re having this targeted therapy or immunotherapy how long do you need to keep having it?

Steven: Look so I think it’s important to differentiate treatment that is aiming at curative intent versus palliative intent, and I guess if we’re thinking about curative intent, it means that we’re administering this treatment hoping that we would increase the cure rate, whereas palliative intent means that patients have incurable cancer and we’re trying improve their quality of life, control the cancer for longer and give the patients more time. Now typically with curative intent treatment, the prescribed treatment would have a finite number of months or cycles or years. In the palliative setting though, when we are trying to control the cancer, there’s no definite set number of cycles or number of months. We just keep going until it either stops working or it’s causing too much havoc in terms of side effects.

Julie: I’ve heard that one of the issues that can happen with targeted therapy is a particular drug might work for a while and then the cancer cells adapt and it stops working.

Steven: Yes, typically. So I guess one of the exciting things that is happening is, you know I said five years ago we were excited about targeted therapy because they were first generation targeted therapies and we put patients on those and, you know, after a year it may stop working, and then we’d go to chemotherapy five years ago. Whereas now we have other, newer targeted therapy to target why the patient’s tumour stopped responding to the first lot of tablets, now we have increasing options in that arena.

Julie: So the benefits of the new treatments, you’ve already indicated fewer side effects generally − if you had to sum up why it’s worth investing in the research into immunotherapy and into targeted therapy, why are these so important going forward?

Steven: Well, because I think there are a couple of things. One is that with targeted therapy I guess we’re more precise in what we are targeting, meaning that the response rate is much higher than blanketed treatments, such as chemotherapy, when we find a target and it can work for a long time. And the other very important issue is that because it’s targeted, as I said before, the side effect profile is much better. So while it can still have side effects, the chance of it occurring is much lower than chemotherapy typically.

Julie: And do some of these treatments deal with cancer, are effective with cancer, where previously there wouldn’t have treatment options?

Steven: Yes, so I guess, for example, in the old days when we look at lung cancer trials, the average lifespan for our lung cancer patients was about 10 months. But now entering this targeted therapy when we are choosing patients with specific mutations such as EGFR, now their lifespan can be two, three, four years − so that’s a clear change. And in the old days without those targeted therapies, people were not, definitely not, living as long as they are now.

Julie: And when you say the old days, what are you thinking?

Steven: Ten years.

Julie: Ten years … right, so very significant change in ten years.

Steven: And I guess the other very important thing about immunotherapy, we are observing very long-term control. So I think that’s the exciting part. While the response rate may not be as high as targeted therapy, if you do respond, some patients can expect very long-term response. So, you know, when you talk to melanoma oncologists, they are seeing, you know, patients who have melanoma cancer that has spread beyond the skin in the liver, in the bones and in the lungs. After immunotherapy, their cancer is completely gone for four/five years, and that is unheard of in the past. So the exciting thing about immunotherapy is that it can have the potential of controlling the cancer long-term.

Julie: And if these treatments are so effective in certain circumstances, why aren’t they offered to everyone as initial treatment? Because sometimes you don’t get them initially is that right?

Steven: Well I guess the recommendation of treatment typically comes from evidence from clinical trials − what is published, what is known. So I guess we don’t know, I guess inherently we would think that if it works later, it should work in the first-line setting or even bring it forward in the curative intent setting, but you know it’s not always the case. And so I think we have to practise what is known based on the clinical trials. Because you have to remember they’re not benign things, they can still go wrong, there’s still side effects associated with those treatments, and if there’s no evidence that it’s going to work better than standard treatment that we have, then I don’t think that it is the right thing to do.

Julie: Just in a nutshell, what is a clinical trial?

Steven: Well, I think a clinical trial is basically an experiment, if you like. It’s an experiment involving our patients, looking at whether this new treatment is going to be safe, effective or better than what we have already.

Julie: Now you’d be aware that some medications are on the Pharmaceutical Benefit Scheme − the government subsidy − and some aren’t. And sometimes people are aware that while these medications are very expensive, if they believe there’s a chance that it may benefit them, people even consider getting their superannuation or even mortgaging their houses or going into debt. Can you talk about access to medications that aren’t yet on the Pharmaceutical Benefit Scheme but which may benefit patients? Are there ways you can get access, either through money or through clinical trials, and if so, what’s the process?

Steven: So I think that is indeed a very difficult situation for our patients. Because on the one hand, you don’t want patients to miss out on the potential, you know, treatment that is going to benefit them. At the same time, you know there are patients that simple cannot afford it and you don’t want patients to feel very guilty for not being able to access, or the family guilty about not being to access, expensive treatment. I guess with a lot of those new treatments potentially you could access them through clinical trials, and that again is a discussion with your oncologist about what is potentially available. It may not be the immunotherapy drug that you have heard of, such as Keytruda, but there could be immunotherapy drugs under development that work exactly the same way as Keytruda. And in that way, you know, clinical trials are all free of charge and you can have the appropriate treatment as required. I guess if there is no clinical trials, then really the only way to access it is through self-funding and in some cases some drug companies would provide some form of compassionate access program. And again the oncologists would be aware of what is available and what is not and often the drug company would substantially reduce the cost, not to zero, but much lower than the commercial rate.

Julie: And so what sort of amounts of money can be involved? Are you able to give us some examples?

Steven: So at the moment, I guess for example, for Keytruda the cost for the drug is roughly $6,000 to $7,000 per infusion and that is given every three weeks. So the schedule in which we give Keytruda is basically one infusion every three weeks.

Julie: For how long?

Steven: So in the palliative setting it’s for as long as it works. I guess the good thing about it is that if you do decide to pay for it, usually after three infusions or four infusions, you’ll get an idea of whether it’s worthwhile continuing, because we’ll know whether it’s working or not. If it’s not working then you stop, but if it’s working it’s great for the patients, but it also means that you have to keep paying for that recurring cost, which is six to seven thousand every three weeks.

Julie: It’s a very challenging situation. I was once with a group of women with ovarian cancer diagnoses for an informal lunch, and people were discussing quite seriously the choice between keeping finance, money available for their children’s education after they were gone, or spending it on extending their life and being with their children, and I don’t think I’ve ever experienced a more challenging conversation in my life.

Steven: Yeah

Julie: And that’s part of your world, I assume, as a medical oncologist.

Steven: Yeah, it’s very difficult, and I guess the other aspect of it is there’s no guarantee as well, and so, you know, just because you’ve spent all this money, you know, we can’t guarantee that the response rate is 100%, meaning that, you know, you could pay for all these drugs and have no benefit out of it and the cancer can continue to grow − which is the, you know, the difficult decision.

Julie: My final question is: the next big things on the horizon, the next big developments, what are we looking at?

Steven: Well, I think there are several things on the horizon. One is combination therapy, so a combination of immunotherapy − so as I said, checkpoint inhibition is what we have now, which has proven to be successful, but we know that some people do not respond to that. And I guess the idea is that the immune system is much more complex than that, and so the idea is that if we add another drug which acts differently to checkpoint inhibition on the immune system, maybe we’ll be able to increase the rate in which patients will respond. So there are lots of clinical trials using that approach of combination of immunotherapy or combining immunotherapy with our traditional chemotherapy, with the idea that hopefully we can increase the rate of response as well as increasing the duration of response. Because that’s what’s important, the duration of response, we want our patients to be here for as long as possible. And I think the other big thing is that we know that invariably our treatment stops working, which is the sad thing, and even with targeted therapy − where, you know, up to 80% of people respond − after a year or so, it stops working. And so now there’s a lot of work in looking at why it stops working so that we can design new drugs to target the reason why it stops working. And I think there’s a lot of push for personalised treatment as well, and I think that is a big thing, I think we’re going to see more and more kind of biomarker driven trials.

Julie: What does that mean?

Steven: So what that means is that we look, we put the tumour through a panel of testing to see, you know, whether there are, you know, we can find this specific change within the gene that may be driving the growth of the tumour, so that we can target it and stop it from growing. So I think that will be something that we’ll be increasingly relying on.

Julie: More precise and more personal.

Steven: Correct

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Julie: That’s it for this episode of The Thing About Cancer. Thanks to Dr Steven Kao for sharing his knowledge and insights.

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Julie: If you’re looking for more information, you can ring the Cancer Council 13 11 20 Information and Support service from anywhere in Australia or go to cancercouncil.com.au/podcasts. If you have any feedback on this podcast, we’d love to hear from you, so leave us a review on iTunes or on our website. If you’d like to subscribe to the show, you can do it in Apple Podcasts or your favourite podcasting app.

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Julie: If you found this episode helpful, you might be interested to know that we’re doing a podcast about genetic tests for people with cancer. We talked to Dr Hilda High about when you might need a genetic test and how genetic tests can be used to match targeted therapies to particular cancers.

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Hilda High: Cancer genetics can provide a lot of information. Particularly if you think it will change what you do or how you do it, then you should try and get that information early.

Julie: Look for that episode Genetic Tests and Cancer on our website at cancercouncil.com.au/podcasts.

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Julie: The stories and experiences contained in this podcast represent the views and opinions of the speakers. They do not necessarily represent the views and opinions of Cancer Council NSW. This podcast contains general information only, and Cancer Council NSW recommends you obtain independent advice specific to your circumstances from appropriate professionals.

I’m Julie McCrossin and this has been The Thing About Cancer, a podcast from Cancer Council NSW produced by Jenni Bruce and Miles Martignoni.

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