Target Therapies for Lung Cancer

Podcast Transcript

Dale Shepard, MD, PhD: Cancer Advances, a Cleveland Clinic podcast for medical professionals exploring the latest innovative research and clinical advances in the field of oncology. Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shepard, a medical oncologist here at Cleveland Clinic overseeing our Taussig Phase I and Sarcoma programs. Today I'm happy to be joined by Dr. Laurie Matt-Amaral a medical oncologist and Vice Chair of Internal Medicine at Cleveland Clinic Akron General. She is joining me to discuss genomics in the management of patients with cancer. So welcome, thanks for joining me today.

Laurie Matt-Amaral, MD: Sure, thanks for having me.

Dale Shepard, MD, PhD: Absolutely. So maybe just to start, maybe you could just briefly tell us kind of what you do and what your role is at Cleveland Clinic.

Laurie Matt-Amaral, MD: Sure. So I'm a general medical oncologist, specializing in anything related to medical oncology, generic general oncology type situations. So we see all types of cancer here, also I'm involved with Medical Residency program here to being vice chief of medicine.

Dale Shepard, MD, PhD: Excellent. Certainly a way that general oncology and lung cancer specifically as well, has changed a lot recently has been the use of genomics. Maybe you could tell us a little bit about how genomics has changed how you practice.

Laurie Matt-Amaral, MD: So genomics has actually played a really big role in how we practice for patients. It actually is becoming more of a personalized medical approach to each patient related to their oncologic cancer or their treatments. Before, we used to have certain guidelines and things that we follow through the National Conference of Cancer Network, and it was generic chemotherapies for certain types of cancers.

Now that genomics has evolved, there are genetic driver mutations, which have led to novel strategies and novel medications that have been made available in all different types of targeted therapies, really starting since about the beginning of the 2000s. And so it's actually made treating our patients who previously have had a whole host of disorders and not a great prognosis, actually made it much easier to treat those patients with a longer survivability and better treatment outcomes.

Dale Shepard, MD, PhD: So in general, what do you find works best in terms of testing and timing? So you can see a patient, when do you normally test? What's the trigger for doing that genomics testing?

Laurie Matt-Amaral, MD: For us in the Cleveland Clinic system, we have a set rule sort of for specifically for lung cancer. For instance, there is a lung cancer hotspot panel that is automatically done. Previously it was done on patients who were only stage 4, or had metastatic disease. Now they have actually expanded that hotspot panel to include multiple common genetic abnormalities for certain types of lung cancer. And it's been expanded to all stages of cancer.

So, it's actually been very helpful in the sense that if you get someone who's a stage I, stage II cancer, and they had a recurrence down the road, you have some of the genetic testing already done. However, if you get someone that you're treating with multiple therapies, maybe one or two lines of therapy in, and you're really just not getting a handle on their cancer, you're having progression of disease, that's one of the ways that you can trigger and do a genomics test.

There are some institutions and there have been some trials where you've done that genomics testing upfront, where you can do it once the patient is diagnosed. There are some pluses in doing it that way, so that you can alter their testing, alter their treatment schedules and their medications that you're using for them right up front once you get that testing back, but it does take a couple of weeks to get that testing done. So, sometimes the feasibility with the patients is also not there because it does cost money and some insurance companies are not covering it.

Dale Shepard, MD, PhD: And of course the patient once treated three weeks ago and telling them that it's going to take two weeks is sometimes rough.

Laurie Matt-Amaral, MD: Of course, and especially if you have someone who's got a disease that really has a burden on their system, waiting for that genomic testing to come back is absolutely not an option. So, you can start people on what I would like to say, "generic chemotherapy" for that disease type, specifically there are really two sets of treatments related to lung cancer with multiple iterations of which drugs to put in and put out and all those things, but you can start them on that and then alter their treatment once that genetic testing is coming back to. So, that gets that anxiety of the patient needing treated yesterday out of the way, but then also personalizes it once you get that information.

Dale Shepard, MD, PhD: And you mentioned before about sort of rules about testing. So are you referring to our care paths for treatment?

Laurie Matt-Amaral, MD: So yes, there are care paths that the Cleveland Clinic has in place, that do follow closely the national guidelines. There are some iterations that are more specific to our population and the things that we see at Cleveland Clinic. Yes, so there is that plan that we do follow and that tries to help make sure that we're following the guidelines for treatment for those patients.

Dale Shepard, MD, PhD: Which actually works out well because you're at one of our satellite hospitals, and really when people walk in to get care at a Cleveland Clinic facility, it's very uniform across the board. So when it comes to testing itself, how do you choose the test? How do you guys go about that?

Laurie Matt-Amaral, MD: It's kind of up to the provider who's doing the testing. I don't think there's one company in particular that testing would be more advantageous through. Unfortunately, sometimes it does come down to insurance coverage, like will one insurance company cover Carers versus Tempus versus Foundation Medicine.

For the most part though, I think it just comes down to preference for the provider. I don't know that there's really been any statistically scientific differences between the different companies who run the test.

Again, some of them may have a faster turnaround time or some of them may have an easier process for getting the samples and running the test. From my experience, I think any of them are fantastic. They'll give you the information that you're looking for.

Dale Shepard, MD, PhD: You mentioned before about the question of when to test and you also mentioned, if patients are doing particularly well with certain therapies, how have you incorporated the sort of a strategy of retesting? So certainly we know, in lung cancer, for instance, you can get acquired mutations. How do you sort of approach, maybe if your test up front, will that look different if I test again after a therapy or two?

Laurie Matt-Amaral, MD: It typically would incorporate retesting. Obviously definitely, if someone has progression of disease on a certain therapy, a lot of the genetic alterations that we see in lung cancer can develop a resistance to those medications that they're being treated with specifically in eGFR and ALK mutations. If you get a patient that's on that therapy, it should be having a response, there are other genetic alterations in that eGFR gene mutation that could be a resistance mechanism that you need to test for specifically. So rather than doing a whole genomic test you're testing specifically for that mutation.

Classically, if you have someone who starts as a stage II or III lung cancer and has progression of disease, if you do another biopsy and let's say they're stage IV disease now you would always retest with that biopsy. At least I do personally, that's my preference because of that potential genetic alterations and that the cancer has a way of mutating itself.

So, what may have been positive before may no longer be positive, or you may have other genetic alterations that you want to target that therapy towards. So, if I've got someone who's got a new stage IV disease, I would automatically test them. As far as sending off a genomic panel, I probably would not test a patient if they're doing well on first line therapy. A lot of times too, it comes down to patients, especially in the community type practice, where we don't really have a genomics test that's on a clinical trial per se that could help the patient get it covered.

Now, most of the companies do have the ability to help a patient in that regard. They have some foundation assistance with that particular test, but I usually save that more genomic testing for somebody maybe first or second line therapy when I'm starting to get to the point where I might not have some great therapies coming up for them, that I have the time to wait that two weeks for a test result.

Dale Shepard, MD, PhD: That makes sense. As a general oncologist, I'm sure you have seen a wide range of diseases with different likelihood of finding the mutation. So, certainly in lung cancer, it's far more likely we find some of the things like mutations and EGFR but there are other things like unknown primaries or colon or other kinds of cancer that they're really uncommon. Any guidance on how do we set patient expectations for, "I'm going to send a test and in two weeks I may or may not have something to offer you."

Laurie Matt-Amaral, MD: Yeah, that's a great question too. I mean, I usually, if it's a specifically a cancer of unknown primary or somebody that it's just something doesn't look right, it's not following what you would expect to see clinically or textbook, which some, most patients do not follow, our textbooks. I sort of give them that information up front and say, "Hey, I have this genomic test that I can send for you. It runs anywhere depending on the test that you pick, 100 to 250 genes. It looks for genetic abnormalities in your cancer."

And they kind of look at me funny usually and say, "Well, wait a minute, genetically, what do you mean? This has something to do with my family?" And so explaining to the patient that, "No, it's really actually the genetics of your actual cancer." But I do point out to them upfront that this is potentially going to be an expensive test.

I don't know if your insurance is going to cover it, but it may or may not give me the information that may help me treat your cancer. Most of the time especially in cancers of unknown primary, most patients are willing to say, I would love to run the test, or can you tell me the name? And I suggest that they call their insurance company to find out what their copay would be, or if it's covered, so that they're not stuck with a huge bill.

But a lot of patients will take us up on it, to be honest with you, because they would like to do whatever it is they can to treat their cancer. And if I have another avenue of something weird or rare or random to treat their cancer, even if it's an off label, compassionate use type of application for the medication, usually most of the time they go for it.

Every once in a blue moon, I'm going to have someone telling me, "Dr. Matt, thanks for offering that to me, but I really am not interested." Or they change their mind when they see that the traditional therapy I'm giving them really isn't helping much.

Dale Shepard, MD, PhD: So the other coverage concerns are certainly real now with the development of newer drugs, like fusion inhibitors, that are really approved across disease types. Have you noted in your practice, maybe an increased willingness of some insurance companies to provide coverage?

Laurie Matt-Amaral, MD: We do have some insurance companies and some payers that will cover more of these NGS Surgenomic sequencing panels, but it's still ... Even if the insurance company and the patient work it out and they do have the coverage and the test is run, on a community side, too. We also run into the difficulty that these patients are then forced to see if their insurance will cover the medication for the genetic abnormality, if there's a medication that exists.

For us it is a kind of a constant struggle to see if we can get free drug assistance. And we have a great staff in my office that does a lot of some of the legwork related to that as well as using the pharmacies, that we send these specialty prescriptions to. And they're very helpful looking for patients for assistance, whether it's through the drug company or a grant for their specific type of cancer, but we also run into the problem of getting that to them and making it affordable and unfortunately, there are a lot of patients who have planned appropriately.

They've done their retirement savings and they just don't qualify for this free medication or help to get the medication and then you're sort of stuck back where you started. You have a genetic abnormality that you know exists for this patient, there's a drug to treat it, but you can't get the drug to the patient. So, that's a real struggle now too.

Dale Shepard, MD, PhD: That's a problem. We have to find a way to fix that.

Laurie Matt-Amaral, MD: I would agree, definitely.

Dale Shepard, MD, PhD: Just off the top of your head. I mean, what percentage of patients do you think get into that position 5, 10, 20?

Laurie Matt-Amaral, MD: I think it's probably about 10 to 15% of the times that we run into that situation. There are days definitely in my practice that I think it's 100%. I just seem to sometimes strike out with everybody for what I want to offer. But I think as we get better about what we're doing to treat these patients and more insurances realize that doctors went to school for a reason and we have all these scientists who are doing all of these studies for us to try to help treat our patients better, then I think they'll eventually get on board with, "You know what, wait, if they have these genetic abnormalities and they fit the criteria, we really should help the patients get this medication." I think it's on its way, but I think it's still a really long process to get people there.

Dale Shepard, MD, PhD: All we can do is keep trying. Right?

Laurie Matt-Amaral, MD: Exactly. Yeah. We keep trying to find the genetic abnormalities, prescribe the drug and see what happens.

Dale Shepard, MD, PhD: There we go. Now, from that standpoint, in terms of choosing therapies, I guess I'd be interested in hearing your perspective as being out in the community. Sort of standard of care therapies and clinical trials, there are not really that much different logistically for our patients because they're kind of embedded within our programs here on main campus, but that might require additional travel, additional effort, things like that for your patients.

So, if you have one of those genetic abnormalities that might be linked to a trial, how do you approach, continue and maybe with a standard therapy versus having a patient come and participate a trial?

Laurie Matt-Amaral, MD: We actually have a clinical trial staff that works for us with us here at Cleveland Clinic Akron general. So, they're actually really great about combing our schedules to look especially for new patients. And then when we have a patient that has a genetic abnormality that we need to find or I've found a clinical trial for whether that's at Cleveland clinic, main campus, or one of the other institutions, either in Ohio or Northeast United States, I usually give the patients that information.

Laurie Matt-Amaral, MD: Most patients are willing to travel, I've not really run into too many that are not willing to travel to Cleveland, to be involved in a clinical trial if there's one open there at main campus. However, if their trial is not open there and let's say it's open at Hopkins or at OSU or any of the other UPFC, they will most of the time travel if it's available to them, or we've done so much as to get them in contact with a person who's either the PI for the study or the study contact and they've actually been able to send their information and either have their case reviewed to find out if they even qualify to make the trip there.

Surprisingly, in a community setting, we do have a lot of patients who are very motivated. I do notice it more in the younger patients, they are very much more motivated to travel to find something. It's not to say that our older population isn't motivated as well, but sometimes there are logistical issues. A family's got to take them there or something along those lines, but we don't really have too many issues giving them that information and letting them decide if they want to do it.

Dale Shepard, MD, PhD: That's great. And I think that it's probably important to point out that given the rarity, particularly of these genomic trials for the mutations, a lot of the trials actually provide travel money and things like that. Hopefully people realize that and look into trials for genomic therapies, because that's how we make progress.

Laurie Matt-Amaral, MD: Right? Well, it's always worth a call. I tell the patients, it's always worth a call or an email to the study chair or whoever the contact is for that particular study, because the worst thing that they can do is tell you no, or you don't qualify. The best thing they can tell you is, "Hey, we'll pay you to come here." Because if it's a rare enough genomic abnormality or a rare enough cancer, they are already scrounging to look for patients, and so there's a lot to process.

Dale Shepard, MD, PhD: That's absolutely true. A very practical logistical question. See how you deal with this, because you have a very very busy practice with lots and lots of patients of various types. One of the things that comes up oftentimes is how do you coordinate the fact that you saw a patient, is sent off genomics and it comes two to three weeks later and sort of doubling back on all of those, have any good tips?

Laurie Matt-Amaral, MD: Be really good at checking your email and your fax machine in your office. Most of the genomic companies that run these tests actually have a physician portal. And so, while I don't necessarily log into that physician portal to get all of these results, they actually do, I'll say double the work, but it actually is a very good double the work. I will get actual emails from the company that says, "Hey, this report is available. Hey, we've got this person's report." And if they don't fax it to me that day, or it's not embedded as a PDF that's secure in my email, I know that I can actually go back and look.

I kind of keep in my head, the people that I send for the genomic test, because I'm not sending multiple people on a daily basis. So, the doubling back for me is not as bad as one would expect. But I usually look at it, make a mental note of what that person's got. If it's something that needs to be addressed right away, obviously it is addressed. For the most part though, I actually review it with the patient when they come back for their next chemotherapy or their next appointment.

So for us, I do a pretty good job of trying to see my patients every time they come for chemotherapy, especially if it's every couple of weeks sort of a thing. Because I'm already looking for side effects and trying to see how they're doing with the treatment. But at that point I can have that genomic test in my hand and go over it with them and show them. And most of them will link the clinical trials to it that are opened for that drug.

So, it's not as much doubling back as one person would think. It's not as if I'm getting the test result, and then having a sit down and call those patients again and have another 30 minute discussion about the results. I'm actually kind of tying it in with their next appointment.

Dale Shepard, MD, PhD: So you mentioned a little while ago, you mentioned genetics versus genomics. And I guess that being the case you're absolutely right. Some people say, "Well, I've already seen a genetic counselor, why do I need to do this?" But what about the tests that come back, and there may be a germline concern. Do you have a system in place that you can link people to the right counselors and get that taken care of?

Laurie Matt-Amaral, MD: Yes, absolutely. So for us in the community, we actually have a genetic counselor that is on our staff down here at Akron General. So we actually send our standard set of cases that fit the standard profile to be sent to genetics upfront.

However, what you're mentioning yes, with these genomic sequencings, they're coming up with a lot of germline mutations and there are a couple of companies that actually go forward and do some of that germline testing for us.

Laurie Matt-Amaral, MD: But if something is discovered, it's a quick call to our geneticists down here, our genetic counselor that we have, and we set them up with her, she talks to them, does all of the family history and then she's plugged in with us. So really easy to get patients in to see her.

Dale Shepard, MD, PhD: So, you have a great setup that sounds right.

Laurie Matt-Amaral, MD: We love the setup. It works fantastic. So she does anything related to cancers and if there's any genomic abnormalities not related to a cancer, but maybe another genetic type disorder, we do use the geneticist and the genetic counselors at Cleveland Clinic Main Campus.

Dale Shepard, MD, PhD: Laurie, I appreciate all of your insight here today. Do you have any additional comments?

Laurie Matt-Amaral, MD: I don't. I thank you for inviting me to do this podcast with you and hopefully some people have some great information and got some great tips.

Dale Shepard, MD, PhD: Well, I appreciate you joining us, and thank you very much.

Laurie Matt-Amaral, MD: Thank you. Have a great day.

Dale Shepard, MD, PhD: This concludes this episode of Cancer Advances. You will find additional podcast episodes on our website, Clevelandclinic.org/canceradvancespodcast. Subscribe to the podcast on iTunes, Google play, Spotify, SoundCloud or wherever you listen to podcasts. And don't forget you can access real time updates from Cleveland Clinics Cancer Center experts on our Consult QD Website, at consultqd.clevelandclinic.org/cancer. Thank you for listening. Please join us again soon.