[ Inglés] A Lung Cancer Roundtable: Takeaways From ASCO 2018

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Topics include: Treatments

Standards are changing in lung cancer diagnostics, treatment decision making, and clinical assessments to a more individualized approach with new medicines and modern technology. What do these advances mean for patients? A panel of lung cancer experts, including Dr. Edward Kim and Dr. Jeffrey Crawford, weigh in on the latest research and treatment developments announced at the 2018 American Society of Clinical Oncology (ASCO) meeting, offering patients hope for more effective treatment strategies with novel agents. The panel shares recent findings on immunotherapies, targeted agents, biomarkers and molecular profiling. Is chemotherapy still recommended as a first-line treatment? What does your healthcare team need to know about your condition to find a more suitable approach to therapy? Watch now to stay up-to-date with current lung cancer news.

This is a Patient Empowerment Network program produced by Patient Power. We thank Celgene and Pfizer for their support.

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Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners 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.

Andrew Schorr:
Hello and welcome to this Patient Empowerment Network program produced by Patient Power.  I'm Andrew Schorr from Patient Power, and we're discussing an update from the big American Society of Clinical Oncology meeting, ASCO, and what it means for patients and family members dealing with lung cancer today.  I want to thank our financial supporters for making grants to support this program, Celgene and Pfizer.  

So we have two noted experts with us.  We have Dr. Jeffrey Crawford from Duke University and the Duke Cancer Institute in Durham, North Carolina, and Dr. Edward Kim from the Levine Cancer Institute down the road also in North Carolina, in Charlotte, North Carolina. Dr. Crawford, welcome to Patient Power and the Patient Empowerment Network.  

Dr. Crawford:

Andrew, thank you.  I'm glad to be here.  

Andrew Schorr:

Dr. Kim, welcome to you. 

Dr. Kim:

Pleasure, Andrew.  

Andrew Schorr:

Okay.  Gentlemen, let's start.  So I walked into the ASCO exhibit hall, which is many football fields wide and long, and I was impressed with so many companies devoted to helping doctors and their patients understand the specific biology, molecular composition of the tumor that somebody might have, for example, with lung cancer. Dr. Kim, is this where it's going, is that sort of precision medicine?  And why is it so critical for patients and their doctors?  

Dr. Kim:

Yeah, thanks, Andrew.  I think it's really important to know how the new standards are changing.  We've been used to a lot of therapies and how we assess folks for decease such as biopsies and histological diagnoses, and now it's not just about that.  It's about trying to figure out what genes exist that are unique to each person's individual tumor.  And we know that these genes are differently made up in different folks, so just to call somebody who has a non?small cell lung cancer, and that's the area that myself and Dr. Crawford cover, is really not the whole picture anymore.  

We've seen this in breast cancer.  We've just kind of come to accept it over the last couple decades, that you're either a hormone receptor?positive breast cancer patient, or your tumor is HER2 positive or not or you're a triple negative, and that's means none of those markers are present.  

Well, we were never that sophisticated in lung cancer, frankly, to have the equivalent of a triple negative even though we did, and we started is seeing this in the early 2000s, especially as we looked at first the mutations like EGFR and translocations like ALK and ROS1, and now that number is just really exploding as far as the number of markers that a clinician has to check just at baseline to make the proper assessment to treat a patient with non-small cell lung cancer these days.  

And that's exciting, but it's also daunting in that the data and the drugs and markers are changing so frequently that it's hard to keep up, and even as an expert it's hard.  

Andrew Schorr:

Now, Dr. Crawford, you're in research a lot as well, and so this multiplying of genes, you keep identifying new ones, right, and then it's a matter of finding out, well, which genes are important at which time for which patient, right?   

Dr. Crawford:

Correct.  As Ed was saying, it's a complicated task, and I think we get now a lot of information.  When we do next-generation sequencing, we get literally hundreds of genes. Some of them are actionable, some aren't, and really understanding which are and which aren't and how to interpret that is becoming a field of its own.  So molecular tumor boards have started to try to dissect this at the institutional level so people can sit down with pathologists, like the pathologist?clinicians, try to work through how to move forward on an individual patient basis.  

Andrew Schorr:

So, Dr. Kim, we hear about immuno-oncology, immunotherapy, and drugs that are being tested in many cancers to try to help the immune system be boosted, I guess, to fight the cancer.  Maybe you could explain that because there was news about that at ASCO, wasn't there, for lung cancer?  

Dr. Kim:

Yeah.  And certainly it seems like every major meeting, Andrew, has news about immunotherapy.  And the really nice part about it, speaking very selfishly, is that there has been a lot of news about immunotherapy and lung cancer, and I get to tease my melanoma colleagues, that, yeah, you know, we know it's been around for greater than five, six years in melanoma. But it required a large scale sort of cancer to take this into the main stream.   

And lung cancer is one of the largest.  It affects so many people out there, and to have these trials testing immunotherapies and these FDA indications, has really transformed things.  What we explain to people is that it's not like the vaccine programs in the past in that the immune system is a very sort of gray area for a lot of folks.  Some people think you can take vitamins and boost your immune system.  Other people think you just have healthy living it will do it, and all those things contribute, because your immune system is really like your micro environment throughout your entire body, and a lot of things affect it, and it affects a lot of things.   

But what's really cool about these newer generation drugs that are impacting the cancer process is that cancers have become smart.  They are able to build up defenses to be sort of stealth inside the body, and so even though there were bad things happening to you your body couldn't tell that they were cancer cells versus normal cells.  And so these new checkpoint inhibitors have focused on trying to break down the stealth or the defenses that these cancer cells have been using to invade the immune system.  

And so now you're really empowering your own body's immune system to fight the cancer.  And that's really exciting.  The side effects, there are some but have generally been very well tolerable.  There are always a percentage of patients who can get a hyperactive immune system, and that's usually what causes a lot of symptoms we see. But all in all—you know, we use Jimmy Carter as a poster child, he's like 150 years old, and he's on an immunotherapy being treated for a stage IV melanoma and doing very well. So that's what my patients see out there, that's why they're asking about it.  We have to select the right people who is appropriate.  

Andrew Schorr:

Well, Dr. Crawford, let's talk about selection.  So we've alluded to testing to understand what's at work or what sort of immune levels, we hear these terms PD-1 and PD-L1, and they're even mentioned on telephone commercials for lung cancer drugs.  So how do we know whether this changing world of immunotherapy applies to an individual patient?  

Dr. Crawford:

Well, that's a good question. So I think we're learning as we go about biomarkers for immunotherapy, but certainly the one that's out there most notably is PD-L1, and so that's a marker of this protein that Dr. Kim was talking about.  It's an immune checkpoint, so PD-L1 when it finds the PD-1 receptor down-regulates or lowers the immune system, and that's a natural, naturally occurring process. It's important so our immune system does get overly revved up, but what happens in cancers it often gets overly depressed and suppressed, so we have inhibitors, drugs that work by inhibiting that reaction that allow the immune system to emerge and attack the cancer.  

So what's really cool about this is that the immune system itself is what destroys the cancer when you take these agents.  This is not like chemotherapy or even targeted therapy where there's a direct cytotoxic effect on the cells.  This is really enabling your immune system to take over and attack the cancer and destroy it. So it's remarkable when we see an X-ray with cancer disappearing based on restoring the immune system.   

So PD-L1 is clearly an important marker, because it's the way these first-generation immune checkpoint inhibitors work through that process.  So one would assume that the PD-L1 measurement would be predictive of who is going to benefit and who is not.  And in some sense it is, but it's not at all like EGFR testing, where we are pretty confident when we have an EGFR mutation we'll have a very high response rate, while with PD-L1 even in patients with expression above 50 percent only about half of them get a good response.  

And on the other end patients with very low response, very low levels of PD-L1, they still have a response of 8 or 10 percent.  So it's not a perfect marker by any means, but it has been helpful in identifying patients likely to benefit.  And what's come out of ASCO is more and more about how to select patients for immunotherapy or a combination of chemo and immunotherapy or other options.  

Andrew Schorr:

Dr. Kim, let's talk about biopsy for a minute or how you get the information from the patient as to what's going on and then what to do about it, if you will.  So getting a lung biopsy is not easy, and I know sometimes there's a problem getting enough tissue to do all the analysis you want, and now we've been hearing about more and more companies that are doing liquid biopsy.  Okay.   

So here's Mr. Jones, you want him to have a lung biopsy.  Would there also be a liquid biopsy or l—and not just at diagnosis, but would you be doing some of this along the way to see if treatment is working?  

Dr. Kim:

Yeah, we've always been attracted to some of the other cancers that utilize liquid tests, ovarian cancer, CA125, PSA, prostate cancer, although we're still not really clear on where we're supposed to be using that to screen patients, but that has given people is principle that they like to follow things.  And that's why cholesterol, for instance, was such a powerful sort of marker even though the relevance of it has been questioned by cardiologists.  People can see there is an effect.   

So, first of all, we have to say that nothing has completely replaced tissue.  That is really the gold standard.  It still is.  I tell our interventionalists, whether it's a pulmonologist, interventional radiologist or anyone, I don't want a diagnosis.  I want tissue.  Because they can make a diagnosis by doing some brushings or some cytology, and they can tell me it's an adenocarcinoma favoring lung.  That is not helpful.  We need to absolutely have data that allows us to send for these molecular tests, which includes, as Jeff mentioned, PD-L1.   

We need EGFR mutation, ALK, ROS1, BRAF.  These are all very important markers now that need to be sent.  And in some cases, at some centers they send for the larger panels. What you get are 3? to 500 genes. I don't need 3- to 500 genes, but there are certainly clinical trials out there that can help match patients into trials based on these genes, so it is some utility.  

But the blood-based markers and the biopsies are improving.  There are definitely very—there are good data that show concordance when they're positive. So if you do a blood test and it shows a positive mutation for EGFR, for instance, you can be pretty confident that the tissue has that as well.  The problem is that when you get a negative result.  And the negative result, those percentages aren't disconcordant, because they really show the amount of accuracy, and so you can't take a negative test at face value.  We don't standardly do liquid biopsies in patients unless the patient really has a contraindication to doing a traditional tissue biopsy.  

As far as the surveillance aspect, as you mentioned, we do that on research.  So on our research studies we do follow patients at every cycle with another blood draw, in addition to what they give in labs, so it's not an extra stick.  It's just extra biopsy.  And we do try to follow to see if we can see some of these different mutations either go up or down based on how the treatment is working or not working.  And we're hopeful that this type of research down the road can lead to more predictive assays that are easier to gather, so we can either surveil patients to see if they have cancer, if it's gone away, if it's come back.   

You can imagine somebody who has been treated for cancer, who has no evidence of disease on a CAT scan but maybe with blood surveillance we can get an early sign if something is coming back.  These are all possibilities and are being investigated, but right now it's really a backup plan if tissue can't be adequately gathered.  

Andrew Schorr:

Dr. Crawford, of course, you're doing research as well.  Do you agree with this, where we are now and where we're headed?   

Dr. Crawford:

Absolutely.  I think what's happened in lung cancer is because of this need for tumor tissue, as Dr. Kim has pointed out, it's really transformed all the interventional things we've been doing.  We were moving in the ‘90s to smaller and smaller biopsies, smaller and smaller needle aspirations just to make a diagnosis, but now we've gone back the other way where we're retraining our pulmonologists to get larger cores of tissues.  They're developing new techniques to get more tissue, endobronchial biopsies.  CT interventional people have been enormously helpful for getting core biopsies, so we get adequate tumor tissue to do the molecular tests we've been talking about.  

So that's really fundamentally important and important to have at every institution hospital across the country.  It's one thing for Levine or Duke to be able to do this, but it really needs to be done in smaller community hospitals and done well by interventional people who can get the tissue we need, because the samples can always be tested at a central site if the pathology labs can't do it locally.  We have to be able to get the tumor tissue.  

Andrew Schorr:

Let's pull this together for a little bit.  I want to see if I've got this right.  So you're having a revolution now in more genes being identified and trying to decide what's actionable, whether you have approved medicines or combinations or drugs in trials, that both of you have alluded to, could for research purposes you identify something and where that could offer hope to a patient where otherwise the existing therapies might not match up?

So what actions should patients and family members be talking about?  And you said, Dr. Crawford, like at the community level or if they have a university hospital as a choice to go.  What should they be doing now? Because obviously anybody diagnosed with lung cancer or their family member, we want the longest life and the best chance right now, and yet you have an evolving field.  So what would—Dr. Crawford, how would you counsel patients and family members so that with what you have available, either as approved therapies or in trials, could be available to them?  

Dr. Crawford:

Well with, first, let me back up a second to say we've been talking mainly about advanced lung cancer.  

Andrew Schorr:

Right.   

Dr. Crawford:

So it's important that patients get diagnosed early.  It's important that patients who are eligible for CT screening and to go that, so we can detect lung cancer at an earlier stage and hopefully offer them curable surgery. And then for them to get evaluated by a multidisciplinary team if they're in early stages to see is surgery alone the right thing, surgery and chemotherapy, a combination with radiation, so all those standards are still present in early-stage disease.  

Now, as we may talk about, immunotherapy and targeted therapy may have a role there as well, but I think our curative strategies remain intact there.  So it's very important to have availability of a multidisciplinary team that can really assess cancer at all stages.  

For the advanced cancer patients then, what's particularly important is for every patient to get molecularly defined tumor testing being done.  So we not only need to know the pathology, as Dr. Kim has said.  We really need to know the molecular phenotype of cancer to really make the best treatment approach for patients with advanced disease.  And in most patients, that should happen before they ever talk about chemotherapy. We need to know are there better approaches for that patient, and we're not going to know that without these tests being done.  

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners 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.

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Page last updated on June 22, 2018