Topics for discussion included:

• Importance of improving clinical confidence and treatment reactions
• Side effect management strategies
• Managing financial toxicity
• Significance of oral therapies during COVID-19

Transcription:

MS. KRISTIE KAHL:Hi everyone.Welcome to today's live broadcast, the "CURE Educated Patient Webinar in Colorectal Cancer."I'm Kristie Kahl, Editorial Director of CURE.We're pleased to bring you this webcast presented by CURE and in partnership Fight CRC and Bayer.

We have a few important announcements before we begin.We encourage you to ask questions during the event which you can submit by typing them in the Q&A box. You will be receiving a survey via email tomorrow. As a thank you for watching the full webinar and completing the survey, you will also be entered to win one of three Visa gift cards.

We are pleased to be joined today by our moderator, Dr. Axel Grothey, Director of GI Cancer Research at the West Cancer Center and Research Institute; Dr. Cathy Eng, David H. Johnson Endowed Chair in Surgical and Medical Oncology, Professor of Medicine and Co-Director of GI Oncology at Vanderbilt-Ingram Cancer Center; Dr. Heinz Josef Lenz, J Terrence Lanni Chair in Gastrointestinal Cancer Research,and Professor of Medicine and Preventive Medicine, at the USC Norris Comprehensive Cancer Center; and Dr. Dustin Deming, Associate Professor at the University of Wisconsin Carbone Cancer Center, and Fight CRC Medical Advisory Board.

Thank you for joining us today and I'll now pass this off to our moderator to begin the discussion.

Importance of Improving Clinical Confidence and Treatment Reactions

Axel Grothey, M.D.:Thanks, Kristie, for ushering this in.We have a great panel here to talk about our favorite topic, mainly management of colorectal cancer.We have kind of a prelim discussion.We definitely have to talk about treating cancer in the time of COVID.That's one of the issues that we'll definitely have to address because there is clearly a need to really put this whole thing with COVID into context of cancer care and cancer care into the context of COVID.

We have some questions that are already here for us to go through kind of in an agenda-like aspect.I want to usher this in by asking Cathy about treatment strategies for colorectal cancer.

We know we have various different treatment options for cancer.We have more intense treatment, less intense treatment.What are the factors that you use to decide what you'd like to offer to patients in their palliative care where they have advanced colorectal cancer?

CATHY ENG, M.D., FACP, FASCO:Some of the items I definitely like to discuss with the patient are basically number one, what is their performance status?I think obviously that's critical for us to determine the best approach to the patient.Also, whether or not they have underlying neuropathy, whether or not basically they're fearful of alopecia or hair loss.Because that's always an issue for some patients, especially depending upon their medication.

Then I do like to ask basically what they like to do in their spare time.I do ask about their hobbies because I also think that's quite important to touch upon.If we have a young patient who wants to be very aggressive and they have a good performance status, we may want to think about FOLFOXIRI, but then in the other settings we can think about FOLFIRI or FOLFOX.But if I have an elderly patient, borderline performance status, sometimes I just start off with 5FU and then build upon it.

DR. GROTHEY:Yeah, so I think the bottom line here is it's not a one-size-fits-all.We take a lot of factors into consideration, patient factors, how much response we need to control the disease, etc.We also I think acknowledge, Dusty, that we can't keep patients on the same intensity of therapy forever.I think sometimes it's important for patients to wrap their heads around the fact that we're trying to make them live with cancer using medicines to control their disease.Can you talk a little bit about this idea of how you prolong treatment duration?Are there treatment breaks that you implement?When do you do that?What about maintenance therapy, oral agents, the whole portfolio of treatment options that we have?

DUSTIN DEMING, M.D.:That's a great question.There are a lot of factors that go into that, similar to the factors that go into deciding the first therapy.You also need to understand the biology of the cancer.Is this a cancer that's very aggressive?What molecular markers are present in that particular cancer?Is it an MSI-high or mismatch repair-deficient cancer and can we think about immune therapies in these patients?We need to understand a lot about how aggressive the cancer is, we need to understand what the molecular features of that cancer are, and then we also need to understand what the goals are for that particular patient.

If it's a setting where we are hopeful to convert that patient to resectable disease, well then maybe in that setting we're thinking about being more aggressive.If it's a case where it doesn't appear that we're likely to get to a situation where we can resect the disease, then it is critical to think about the strategy of how we're going to use therapies over time.We often think about starting with chemotherapy knocking down the cancer to a significant extent, but then thinking about ways that we can maintain that response.Can we think about local therapies?Can we think about targeted therapies?Can we cycle those therapies over time, hopefully not exposing the patients to many side effects all at once, but kind of gradually targeting the cancer over time?

DR. GROTHEY:I mean when I talk to my patients, I use terms like, "I'd like to use the least amount of treatment necessary to control the disease."That is really where we are, so turning the cancer to chronic disease.

Heinz, Dusty already talked about biomarkers.I know that's a field that is of a little bit of interest to you.How important is it for patients to understand what their kind of genomic makeup is of the cancer?How important is that for them and for their treating provider?

HEINZ JOSEF LENZ, M.D.:Yeah, I think it is extremely critical in order to really fully understand the picture beyond what we know from the imaging, what we know from the labs, what we know from the performance status, as already mentioned.I think if the treatment goal is established--and I think that's the most critical decision.What do you want to reach or achieve with your treatment?Resectability, symptom control.Is there any way to use chemotherapy you can use for a long time without any dose-limiting toxicity?

One of the factors to decide what the most effective or most appropriate treatment is, is really understanding the molecular makeup of the tumor.Because we know with certain biomarkers we have different treatment choices.That actually may impact not only the first-line treatment, but maybe also the maintenance part of treatment.

I think it will give us choices between target agents such as cetuximab, the antibody against the EGF receptor.It will give us choices of immunotherapy in first line when you have MSI high.It also kind of sets the tone for subsequent treatments.

Because right now we are talking about potentially scaling that down, the intensity of chemotherapy, to maximize the benefit.But I think we need also to be considerate of that if the treatment doesn’t work, what is our second line of treatment?How do we switch quickly?We have also seen that certain markers are highly prognostic like BRAF mutations.We need to know that relatively early to be ready to switch quickly without further delays of molecular testing.

DR. GROTHEY:Yeah.I think that highlights one of the challenges we are facing because we see patients on treatment or living with active metastatic disease for years.For years.That of course creates challenges in terms of side effect management, when you implement treatment breaks, what the importance is of rechallenging treatment using reintroduction of chemotherapy approaches.What's the role of the oral agents we have?

Cathy, can you make the me and the audience understand: what is a good candidate for you, where you think let's stop treatment for some time, watch and wait, and how closely are you following patients when they implement these treatment breaks?

DR. ENG:You brought up something that's very important.Obviously we need to take into account that patients can't be on treatment without any breaks for a prolonged period.We do need to take into account that before COVID they would normally have times where they would go vacation with their family, enjoy time with their family, and that's very, very important for these patients as well.

For a patient that I give a treatment break, I probably will bring them back depending upon the event of the tumor burden in all fairness and depending upon if we have somebody with extensive disease involvement in multiple places, where it's somebody with only lung-only metastasis.That also makes a difference.

But my tendency if I'm going to give them a treatment break, the longest I will give them a treatment break for is maybe six to eight weeks.That may be the case for somebody with lung-only metastasis.Some patients that have been with me for many years, because I know the biologies of the tumor and how indolent it may or may not be, sometimes it let it go for up to three months.That's [break in audio].

DR. GROTHEY:I think the more we understand and know the patient, know tumor biology and have already followed patients, the more flexible we can be to kind of make these calls about treatment breaks, holidays.I do believe patients really sometimes emotionally and physically benefit from exactly that.

Heinz, just come back to because I see a chat window here with some questions.With all the new immunotherapy treatments, what should my tumor be tested for?It's kind of a check card.What should patients know what their cancer should be tested for?Let me ask you right up front and perhaps in later lines of therapy.What do you think?

DR. LENZ:I like to do the best testing up front at the time of diagnosis with a panel I can get the next generation sequencing panel, which covers 500 to 700 genes, includes all the important ones, including some we still don't know how to treat, but I think the area of research is evolving very fast.I think what is absolutely critical to know: KRAS and NRAS, BRAF, MSI high, BRAF, NTRK, and HER2.Because these have already treatment options which could be used first line or relatively quickly in the lines of treatment.You do not want to pause with a fast-going tumor and wait two or three weeks for a test to come back.That creates unnecessary stress.

I think the target agents we have available, you should know up front at the time of diagnosis.That saves you a lot of time and anxiety, that you basically can create a treatment plan B on first line.I think NGS testing is approved in the U.S., so it should be accessible for most of the patients in a way that they can get a full understanding of their makeup.Also in academic centers we all have clinical trials for new targets, which may not be part of our NCCN guidelines with genes, but it would be very important to know also to look for clinical trials for certain genetic alterations.It's very important to do the best genetic testing possible.

DR. GROTHEY:Yeah.I completely agree with that.For immunotherapy specifically, I think the low bar would be MSI high or mismatch repair deficiency, so that’s either through next generation sequencing like you said, PCR reaction, or immunohistochemistry.It has to be done in every cancer independent of stage and age.I think we all know that, and this is critical for us.

Then we have NGS panel, next generation sequencing panel, that can also find other cancers that are immunogenic like the POLE tumors, which exist.Heinz.

DR. LENZ:Yeah, and I think what is new on the block of the biomarker is the tumor mutational burden.A lot of people still don't get the test or don’t know what that means, but it is basically the frequency of DNA mutations in the tumor.Since June, the FDA approved monotherapy for a TMB of 10 or higher.I think that is important to note because I still see some patients referred that have a TMB of 20 and were not considered for immunotherapy.I think that needs to get out, that people know or patients know that there is a marker, which they should ask for if it's not done, particularly if the test was done a year ago and it was not part of the panel testing.

Side Effect Management Strategies

DR. GROTHEY:That's a good point.Let's talk about side effect management.Dusty, when you talk to a patient about side effect management--again, we already identified patients are on treatment for a year sometimes--what are the guidelines?What do you tell them initially so that they know what to expect and perhaps particularly when they start let's say an oxaliplatin-based regimen?

DR. DEMING:Starting with oxaliplatin, I think it's really important to counsel on the cold sensitivity and also the neuropathy.Being in Wisconsin and winter starting here, cold sensitivity is a big issue for us.Nobody gets into their car and drives without understanding cold sensitivity when they're on oxaliplatin here.

Making sure that patients are aware that that's going to happen is I think critical to the management there.Because if patients know about the cold sensitivity, wearing gloves, scarves--actually, the masks have been a great help for our patients with COVID.Breathing cold air is not nearly the issue that it once was.

Then from the peripheral neuropathy with oxaliplatin, understanding the difference between the cold sensitivity and the neuropathy I think is important for the patients.That way they can help alert us as oncologists about when that neuropathy is starting.Because it's really critical for us to understand the symptoms the patients are getting, so that we can control how long they're on the oxaliplatin and what doses of oxaliplatin we're using.Because that unfortunately is one of the major life-altering toxicities of the treatments we give for GI cancers and unfortunately can be permanent for many of our patients.

DR. GROTHEY:Yeah.I mean that's one of the reasons why I feel very strongly about limiting the initial duration of therapy.You don't treat to toxicity; you stop before toxicity hits, the neurotoxicity.Because it's not necessarily always reversible once it is established.

Have any of you heard about icing during oxaliplatin infusion?Cathy, you're nodding.Have you tried it?

DR. ENG:Have I personally tried it?

DR. GROTHEY:No, no.In patients.

DR. ENG:Yes.A couple of my patients have tried it.Once again, it's a couple of patients because they'd seen it on colon blogs.A couple of them do feel that it may be beneficial.It's harmless.I have not been against it, so I told them if they'd like to try it, go ahead.But I think anything to potentially reduce the neuropathy that may ensue for patients would be very helpful, especially if you're going to use the CAPOX regimen in combination with Xeloda.Sometimes the patients get confused between the neuropathy and the hand-foot syndrome that can be significant for some patients.Because they have that sandpaper feel on the bottom of their feet.Anything to reduce their symptoms so they can tolerate their treatment better, I'm all for it.

DR. GROTHEY:I actually used icing in my patients--

DR. ENG:[Interposing] They've tried it--

[Crosstalk]

DR. GROTHEY:It actually does seem to work.Quite interesting.Some patients are real true believers.My nurse, Amber, is actually quite involved in that.She's a believer in icing, so I would never contradict my nurse, of course.She's a believer; I have to be a believer.Because she goes in to ask those patients very, very closely.

There's a question about memory loss.Do we see memory loss as a permanent side effect of chemotherapy?I think it's commonly also known as chemo brain.Dusty, what do you think?Is that something you point to?

DR. DEMING:Memory is a very complicated issue regarding cancer and chemotherapy.Many of our therapies do cross the blood brain barrier and have the potential to impact the memory.However, even hearing the word "cancer" for many of our patients has been shown to impact their memory.When you're dealing with toxicities and fatigue, in addition to potentially some direct effects from the chemotherapy as well, it can be quite an issue.Many patients do describe this as a real thing.

The things that seem to benefit the most for this are things that help with mood, so being active, good social support structures.People who are working who continue to work, that seems to be helpful.Time away from chemotherapy obviously could also be helpful as well.

DR. GROTHEY:It's interesting.I remember there was a study in breast cancer where this topic has of course been discussed quite a bit.There was a study in breast cancer that chemo brain hit patients even before they had chemotherapy, just by having a diagnosis of cancer.Not to kind of minimize this issue, I think it's an even worse issue because just being diagnosed with cancer has a huge impact on our ability to focus, etc.It really takes over people's lives.It's cancer brain.It's kind of a cancer diagnosis brain.

There's a question about what is icing.Okay, so icing initially sounds counterintuitive because we tell patients you should ice, ice exposure or cold exposure after oxaliplatin.Icing was developed actually by patients and was in these chat boxes, Colon Town on Facebook and others.During the two-hour infusion of oxaliplatin, patients put their hands and feet in kind of ice water, ice socks, kind of coldest water, and suck on ice chips during the infusion.They really wrap ice around their hands and feet and suck on ice chips during the infusion.

It's interesting to see as patients who did it one way and the other switched over kind of a crossover study, and they do tell me that it's quite beneficial for them.I mean again, I would encourage you to try it, but not every patient is affected by the cold sensitivity in a similar way.I've seen patients who really didn’t like, particularly someone who's spent 15 years in Minnesota when patients kind of walked out of Mayo Clinic and they took a deep breath.It's not just the skin.It's also the airways that get affected in the lining of their mouths, etc.

The icing is from what I know not beneficial to capecitabine/Xeloda.This is a very different mechanism of action.But I really appreciate, Cathy, what you said, which was some patients when they go from let's say oxaliplatin therapy to capecitabine-based maintenance therapy, they still have sensitivity to their hands and feet because it's an overlap between the neurotoxicity and the skin toxicity.I think that's sometimes not easy for them to tease out.

There's one question that I saw in the chat too.What about DPD deficiency, Heinz?Would you think that every patients needs to be tested for DPD deficiency up front?Because there are some European countries--and you might want to explain DPD deficiency actually is--where it's mandated that patients receive testing for their DPD before they even get 5FU.You might want to say what that is.

DR. LENZ:Sure.I think DPD deficiency is an enzyme which basically breaks down 5FU or the fluoropyrimidines.If you do not have the enzyme, your cytotoxic 5FU or fluorouracil or fluoropyrimidines remain in the body.Because then you cannot get rid of it, it can cause significant life-threatening side effects.

The Europeans presented data that when you do it and you identify these deficiencies, you may prevent some toxicities.But there is a lot of controversial discussion around it.We just published a paper with Dr. Genti [phonetic], about the real basis is for DPD deficiency should be tested.

I think the advantage is that you can really identify early on the ones who have life-threatening toxicities.These are extremely rare, but there is a little bit of false assurance that when you do the test, you're okay.That's not correct because you test about only for one-third.Not all the mutations DPD are the same.For some you can reduce half, others 30%, others you shouldn't do it.It's a little bit of a confusing field, given your false assurance that when you tested, you will be okay and you don't have to monitor it.

Now I do not do the testing on my patients.It's an extremely rare occurrence.Since we all use 5FU as an infusion, if there are symptoms developed, you can detect it relatively early.The hallmark effect is that you have significant side effects with the first dose.In the first day or two you see the side effects.I get a lot of referrals to work up DPD deficiency when the patient is treated for a couple of months.I tell you, this is not DPD deficiency.

I think we need to learn and the oncologist that it's a really complicated field, so I don't think it's necessary to test.You should be just aware about the side effects and how they occur.If it happens in the first cycle, I would get very suspicious, particularly that the typical side effects are not the nausea and vomiting.It will be a lot of CNS symptoms, but that's not chemo brain.These are side effects of the chemo directly on the brain.

I think we need to be aware of it, that we can test, but I have not routinely used the testing to make any treatment recommendations.

Managing Financial Toxicity

DR. GROTHEY:Very good.The whole idea about toxicity, toxicity management, I think more and more we also need to include financial toxicity in that.I mean people who like Dr. Len Salzwin [phonetic] said, we need to really list the financial toxicity in kind of a grade if I mention toxicity to our patients.

That's an interesting phenomenon actually for someone who came out of a German system where there is literally no financial toxicity for cancer care, and patients don't get bankrupt from cancer.But it's a real phenomenon here.I have a lot of patients in the Memphis area who are uninsured or underinsured.

Cathy, do you communicate about financial toxicity to patients?Do you take that into account?I think it's a double-edged sword.We want to give our patients the best treatment possible, but we can't ignore some of these issues too.How do you deal with that?Because I have no good way to deal with that myself, to be honest.

DR. ENG:You're asking a great question.Yes, it is a concern for patients, obviously.Because this is a real problem for them, especially depending upon where they are in their lives, whether or not they have prepared for this type of potential impact on their health.It's a big issue.I think our center very much probably like your center, every time we decide to initiate a chemotherapy regimen or any type of treatment regimen for that matter, we could document everything.

We make sure that everything is in the note to potentially support why we're making these decisions.Then that hopefully will support why the insurance provider will approve that decision.As you know, it varies depending upon the insurance provider.Of course, there are those that are uninsured, which is an unfortunate situation because that makes things much more complicated.

I think social work is extremely important in this setting in helping try to find financial services as well.

DR. GROTHEY:Dusty, what do you think?Do you perceive that as an issue?How do you deal with that?

DR. DEMING:I mean it's become a major issue.One of the complicating factors is that it's very hard for us to predict for any individual patient ahead of time before we submit a prior authorization who's going to have large copays and who's not.Some of it depends on the particular drug.Even from the same drug companies, patients can have different plans, which makes it really complicated.Every time we're thinking about changing therapies for our patients, they're actually meeting with our pharmacists to talk about what the plan is for how we're going to get that drug for that patient.

Unfortunately, it does result in some delays.What I'm trying to do now is actually predict that a patient may be getting close to needing to change and start thinking about prior authorizations even before they have disease progression or before we're thinking about switching to maintenance therapy, just so we have some lead time to get those approvals.

DR. GROTHEY:Heinz, do you think this issue has gotten worse, the idea of how many preauthorization calls you're taking.I don't know whether you're taking them, the so-called peer-to-peer idea?Is that getting worse or is it kind of stable?What do you think?

DR. LENZ:Yeah, I think it's a very diverse field because USC runs the county clinics, the county hospital, which is basically uninsured of every fully-insured patient population.Here you have almost fewer problems.The county covers the cost.Not all medications are approved, but most of them are, so there are not major gaps of treatment.That is okay.For the private patients with HMOs, we have the most problems, particularly for all medications, that the copay is suddenly $2,000 or $3,000 and patients cannot afford it.

Here what we do is we are trying to get of course the private insurance with peer to peer and so on, but we also take fully advantage of having a full-time person only for compassionate use to do other paperwork to get the companies to pay it for basically no copay.

Then we have one area for patients who are on clinical trials, who have to come in five times a week or much more often than scheduled, which can be a big financial burden, particularly when they have to stay overnight close by.

There is a foundation on the West Coast called Lazarex Foundation.It's at USC and UCSF and other institutions that will pay the travel and the lodging and everything for the extra visits for clinical trials, which has been incredibly important for us, particularly for the county patients for which travel is a big, big burden.Because many of them take busses and it's not easy for them to come to us at 7:30 in the morning.

I think it's very complex and it seems like it is not really a system you figure out what to do because it changes every week.One time it's approved; the next time it's not approved.Then it's peer-to-peer; then it's not peer-to-peer.I think patients need to understand we are in a very difficult situation where there are basically changing rules on a daily basis where we get approval and then not get approval, and it seems like we don't know what we are doing, but it's actually dictated by insurance carriers.

DR. GROTHEY:Yeah, and then I hear the complaint, "Why can't I start right away?"We try to really mitigate the--of course we can start right away if you pay for it, but we try to be mindful about that.I sometimes have to really lower expectation because we want to make sure that patients are not experiencing the financial toxicity as much.

I know what you mentioned, the oral medications, copays for oral medications.Because we're using oral medications more and more, which are targeted agents, oral chemotherapy.This is definitely a whole in the way patients are insured to a larger degree.

Cathy, I know you're very interested in young patients.I mean when patients reach Medicare, I'm actually, "Yea, Medicare.That's great."Because then you have actually less of an issue.But young patients are commonly not even insured.They think they don’t need it, but we see a surge actually of younger patients right now in our clinic.I know you are very interested in that too.

DR. ENG:Yes, without a doubt.I mean that's a big concern for young patients.It adds to the stress on top of everything else for them.

DR. GROTHEY:Yes.I mean I'm someone again who grew up in a system where money didn't matter for healthcare.I always feel sad when patients have to deal with their cancer diagnosis, cancer treatment, side effects, and also try to avoid financial harm, not just for them, but also for their families, etc, and this is a big issue.Communication about these issues I think is critical.

DR. ENG:Do you think that biosimilars will have any impact in the future?

DR. GROTHEY:Biosimilars will definitely have some impact, but biosimilars are IV.I think that's not the main issue.I think it's more the oral medication copays that we see, the specialty pharmacies that get involved.Everyone takes a cut and just recently there was an article actually in the Wall Street Journal about that.What are the components?Why get healthcare?Is healthcare more expensive now than it was let's say 5 years ago, 10 years ago?It's not what we do.It's drugs, procedures, etc, and that's frustrating to see.Heinz, you want to say something.

DR. LENZ:I think what has been becoming increasingly frustrating is besides the chemotherapeutic drugs, we have more and more troubles with pain medication, that they refuse to pay for fentanyl.They refuse to pay and I'm thinking this is really, really highly concerning, that we're suddenly struggling to get the pain medication to patients being paid for, certain nausea medications or EMLA cream.I mean this is completely sometimes out of control, where we have to go back and I send them to the 99 cent store for the lidocaine.I mean this is like I don't understand how this all changes and who is in charge of it, but it's very, very concerning.

DR. GROTHEY:Anti-nausea medication too because we have effective anti-nausea medication.Sometimes we can't give them to our patients.I mean it's all an issue.

Significance of Oral Therapies During COVID-19

DR. GROTHEY:Let's switch to COVID-19, which was COVID-19 was covered in 2019, coronavirus.Dusty, how has COVID affected how you treat patients, when you treat patients?What are the issues that you're dealing with right now?

DR. DEMING:With COVID-19 it's really affected how it treat patients in just about every potential way.I mean even what we were just talking about with financial toxicity, it used to be that our institutions were in a place where a few cycles of therapy was something that if they had to, the institution would cover.But as the institutions become financially strained, that is becoming harder to come by that type of assistance.

But when we're talking about treatment for our patients, this is kind of another layer of that initial conversation we had.Where we were talking about the goals of the patient, the aggressiveness of the cancer, now we also have to understand kind of our local pandemic and what's going on with COVID-19.

Is it safe for my patient to get the therapies that I would otherwise want to get them?Are they in a social situation where they can be supported or are they going to be completely isolated?Are they living alone and won't have the support they need?Is there someone who can help get them to and from appointments?Are they able to socially distance?Are they working in an environment where they could be at increased risk for COVID exposure?All of these things now have to play into our decision of how we treat our patients.

Fortunately, even though there is an increased risk of complications from COVID-19 for cancer patients in general, with most of our therapies for colorectal cancer we're fortunate in that it doesn't appear that the immune system is suppressed to the extent where there is a dramatic increase in risk of either acquiring COVID-19 or complications from COVID-19.But definitely it's something that has to play into our decision making.

DR. GROTHEY:Cathy, have you changed treatments, switched to oral medication, increased treatment intervals?How have you dealt with that?

DR. ENG:Definitely.I think almost everyone, not just our institution, whenever there is a potential option and if we believe the patient's going to be able to tolerate the treatment and will be adherent and comply, we have changed to oral medications if possible.Also if you're receiving the infusion of 5FU, obviously I think many of us have removed the bolus 5FU as well, which also reduced the myelosuppression or the reduction in the counts, the possibility of that happening for the patients.

Then I have to admit that normally before when we would be considering an aggressive regimen such as FOLFOXIRI, before we would wait to see if the patients' counts may or may not drop.Because it doesn't happen to everyone.But now we're going ahead and giving them Neulasta, as long as it's paid for once again.So once again, an insurance provider issue that must be addressed.But we are providing that up front because we want to reduce the patient's risk as much as possible.

Then obviously for those that are receiving oral medications, the use of telehealth.We've been basically incorporating that a lot as well.

DR. GROTHEY:Heinz, oral chemotherapy, oral cognitive agents in management of colon cancer, how important are those?Where do you use them?There's actually a question that came up.How do you know that patients are compliant?Is there a compliance issue?In both ways.Because I've seen patients who kind of try to double up once they've missed a dose sometimes.How do you communicate that do you think?

DR. LENZ:We talk a little bit about the toxicity before and I think absolutely critical is making sure that the patient understands what will happen, what side effects can happen, what they can do about it.Because I think the more informed they are, the higher the compliance is, and they will know what to do and hold it and treatment.I think there are certain drugs we know exactly what happens, such as capecitabine or regorafenib.We tell them that this happens; just stop it.With that, we have not really seen an issue with compliance.

I think sometimes what we see in our county clinics because almost no one speaks English in these clinics, to make sure the translation is correct, that they know to take three weeks on and one week off and not four weeks on.Because sometimes we get phone calls that they're running out, but they shouldn't run out.I only give it for three weeks.I think language issues could be a problem and I think it's very important to have an adequate translator because sometimes family members do not understand and don't translate correctly.That's what we have experienced.

I think that cancer patients overall are usually very compliant when they understand why we're doing it, for what reason we are doing it, what the potential benefit is.I have no major issues using it in compliance, even depending on the social background or the financial situation or the education status because people understand the importance of treatment when they have active cancer.

DR. GROTHEY:[Crosstalk] you mentioned--go ahead, Cathy.

DR. ENG:I just want to mention I'm just very careful with Lonsurf.That's the one, the five days.That has been an issue for a couple of my patients.

DR. GROTHEY:Trying to figure out how to dose it.I would pass a note to Lonsurf.For me, my own perspective, always start on a Monday to make this happen.

DR. ENG:Me too.

DR. GROTHEY:Otherwise, they get messed up.It's such a strange way of dosing things.

DR. LENZ:You know what happened with us?Now we're giving it usually with bevacizumab.I'm sure you're doing that too.That secures them a little bit that they don't take it longer.[Crosstalk] that helped managed these patients.

DR. GROTHEY:Yeah, I agree.I agree.Our Danish colleagues helped us here quite a bit.

Heinz, you mentioned regorafenib.The problem that I see with some of the education that we have to put into these discussions with patients, the more complicated the education is--I mean and regorafenib and capecitabine actually are complicated drugs.I mean it's not just the dosing, but also understanding the side effects, really sitting down and thinking about the velocity, what can happen, voice changes, skin rash, fatigue, those kinds of things.It takes a long time if you do it right.

I hope you and I'm sure that a lot of us have dedicated educators that actually sit down with patients.But I don’t think this is guaranteed everywhere.I think the critical issue with ensuring compliance and understanding about side effects and management is you just don't write a script and hand it to patients.Four pills a day; three weeks on, one week off.Come back in four weeks.That’s probably the worst case scenario.It takes time.

How can we make sure or what would you like to see--Dusty, from a Fight CRC as a resource--that patients get educated about these things, that we have the education actually in place with these more complicated treatments?

DR. DEMING:I think that's absolutely critical.Really, Fight CRC has actually great resources for a lot of the topics that we talked about today.Side effects for particular therapies, especially how to handle different rashes from different therapies, Fight CRC resources are great for that.

They also have resources though for financial toxicity and even understanding how COVID-19 might impact your treatment.All those types of resources are available on the Fight Colorectal Cancer website and would definitely point patients to that website as a great resource for that kind of information.

One thing that we've actually found that has been really helpful with education patients is actually we have our pharmacist call them five to seven days after their visit when they started the therapies.That's really when they actually are more receptive to the education.Because they've started to understand some of the side effects they're going to get, that initial shock of my cancer situation changed and I'm starting a new therapy.That has kind of settled down to some degree and they can kind of start to better understand how to manage the side effects.That’s something that we do at our center that's really been helpful, is just kind of checking in with the patients by phone usually a week later.

DR. GROTHEY:I think that's also what Cathy mentioned, these telemedicine visits can come in, oral medications, and just checking with patients.Once they know what we've talked about before I mean in terms of you might tell them about the side effect, but it becomes more real after the first week or two of treatment.I think it's very critical.

I like the fact that we have these telemedicine options for select patients, although I still believe in the end nothing beats face-to-face contact.It's just there's more that's conveyed than just talking and doing a video chat.I think that's it.Although, I hope that we will keep this option of telemedicine hopefully across state lines.That's another issue that I would love to tackle.Heinz, you know about this.

DR. LENZ:We have the technology and now we are limited by the liability issues from one state to the other.I think that is something we need to address on a national level.I think we have the opportunities.This is all when they would fly to the state; it's possible, but not when they call in.It just makes no sense to me.They ask then: you need emergency medical license in Tennessee.Really?Okay.I think somebody needs to look into that to allow more adequate access to patients for their physician.It's a little bit sad that we are coming so far and then we cannot do it.

DR. GROTHEY:I completely agree.It's a United States Medical Licensing Exam, USMLE.Then it still gets broken down to an electoral college and there's no popular vote.Anyway, that's an issue.Long history, etc, but I think it's critical.We should learn from that.We should learn from COVID.We should really take some of the things that really worked into the future to make healthcare better and more affordable too.

Any--Heinz.

DR. LENZ:I think for telemedicine, the best for us is the multidisciplinary tumor boards.Now the surgeon's called in from the O.R.Before they said I cannot do it.People are more able to call into this meeting, so this is actually a much more fun meeting and everybody is actually on it, almost too many.Because everyone is able then to use even 10, 15 minutes to call in when they have a question.That was not there before.

DR. GROTHEY:I can actually see the scans better because they're right in front of me.You can actually really see what's going on.

DR. LENZ:That's true.

Q&A

DR. GROTHEY:There's a question about another hard topic.I mean I think the hard topics this year are immunotherapy--how to beat immunotherapy--and circulating tumor DNA, which is of course a very interesting aspect.Dusty, liquid biopsy, ctDNA.I know you're involved in some of the clinical--I think we're all involved with CTD, the research to some degree.Dusty, do you use it in your clinical practice?Let's focus on the earlier-stage setting.Can something like a ctDNA test substitute for scans let's say in the followup for patients after surgery?

DR. DEMING:I don't think we're to the point where we can substitute for scans, but I do think that there is a place now and I think there's a growing place for circulating tumor DNA in the identification of molecular residual disease.Where I think the obvious place is right now, is for those patients who you wouldn’t otherwise treat with chemotherapy.

If they have molecular residual disease or a positive ctDNA test, what's that telling us is basically those patients are destined at some point to have their cancer recur.The big question in the field is what happens when we give them chemo.Now I think there's growing evidence that it does seem to be that for patients we can actually clear their ctDNA.Now we need longer followup on those patients to see what actually happens, but I do believe that we likely can cure some patients by identifying them as having molecular residual disease and treating them with chemotherapy.

One of the studies, the COBRA study that's ongoing right now, is I think a great use of this type of technology, looking at if we have a patient with molecular residual disease and treat them with chemotherapy, will that be helpful in preventing their cancer from coming back?

Now I think there are a lot of questions that need to be answered.Can we actually reduce the intensity of chemotherapy for some patients based on these tests?In my own opinion, I think we're getting closer to that.I'm not quite ready to do that outside of a trial, but I do think we're getting closer to that and I think very soon we'll have data that will help us kind of risk stratify.

It may be that what it does is it changes the percentage of benefit for a particular patient in a particular setting so the patient and the physician can have a better discussion about what the benefit is of the chemotherapy and the kind of the risk-benefit ratio.I think ctDNA could help that.But outside of a clinical trial, I'm not quite ready to reduce the intensity of therapy for patients yet who I otherwise would give chemotherapy.

DR. GROTHEY:I think that's a great distinction you made.It's an easier call to treat when you would otherwise not treat based on the MRD, based on the liquid biopsy test.It's a different issue to not treat where you normally would treat based on the negative test.I could imagine--I think we're on the same page on that--that eventually we will have data to show that we will do sequential ctDNA testing and only treat when needed.We have kind of a delayed adjuvant therapy when we see that the molecular test turns positive, but I think we need more data exactly for this topic.Because I mean in the end it's the Holy Grail of identifying patients who really need adjuvant treatment.That would of course be great because the toxicities we could spare patients would be tremendous.

Cathy, there's one question--go ahead.

DR. ENG:I was asking something.I just want to make sure that the listeners in the audience understand that Dusty mentioned the COBRA trial, and that is specifically for stage 2 disease.That’s important for patients to enroll on to it.Because for stage 2 colon cancer, it's a very great area for us as physicians, as well as the patients.Then there is a trial coming up with energy and supported also by our colleagues, Chris Liu [phonetic] for stage 3 that should hopefully be open early next year as well.

DR. GROTHEY:Again, this is really trying to test the utility of ctDNA and really answer the question that came up prospectively in trials.This is the level of evidence we need in order to really be able to recommend treatment for our patients or no treatments.

Cathy, there is an evergreen question, supplements.A lot of patients go: What can I do?What do I need to do?I take my vitamin D.What do you tell patients then they ask: are there any things that I should take to improve the immune system, to help with side effects, whatever?

DR. ENG:I think the one thing that for many of us following--at least for early stage patients, I think a lot of us probably recommend a baby aspirin.I think that's commonly recommended by many of us.But in regard to the multiple supplements, I have no trouble of considering supplements, as long as it doesn't interfere with the chemotherapy.That may be not only supplements.Sometimes it can be teas as well.I've seen some very dangerous side effects on the liver from some very benign-appearing teas that over-the-counter.I've seen significant impact on liver function tests.

I tell all my patients: please tell me about your herbal supplements.I actually am supportive of some.Please run it by me so I can run it by our pharmacist.Because we have to be very careful depending upon what treatment they may or may not be on, so I think that's very, very important as well.

DR. GROTHEY:I've actually also seen hepatitis or liver damage from some Chinese herbs or some mushroom cocktails.There's so much out there and the problem is you can find anything you want to find.

DR. ENG:That’s not just Chinese herbs.[Crosstalk] other types of herbs as well.

DR. GROTHEY:Okay, let me qualify that.It's not just Chinese.It should be region-independent herb probably now.I hear you.It's coronavirus.We know that too.It's not another region-based virus.

But I like the idea that you brought up with the baby aspirin.I think is something where we at least have some epidemiologic data that might actually help, particularly in the secondary prophylaxis of colon cancer.There's a lifestyle discussion I actually have with my patients when we sit down after adjuvant therapy is completed and we say: what do you do from now on?I talk about physical exercise.We do reduce red meat intake.You should reduce your alcohol intake.A baby aspirin comes into play there too.

Heinz, there's another question again about qualifies and disqualifies a patient for immunotherapy.I want to preface that by saying that in the metastatic setting, the stage 4 setting, only about 4% to 5% of patients really qualify for immunotherapy right now.Heinz, again, who are these patients?

DR. LENZ:We know from clinical trials and the approval of immunotherapy for patient population with colorectal cancer and any other cancer who qualifies who have microsatellite instability, which means an instability in the genome caused by a DNA mismatch repair.It's very complicated.It sounds it, but it's really usually associated with mutations of certain genes, which repair DNA, and we call them mismatch repair.

But there are others who can cause also this instability.We know with this instability we have significant efficacy when we use immune checkpoints, basically stimulating your own immune system, enabling it to recognize the tumor cells.Because of all this extra instability, they have proteins which are recognizable by taking away this block by the immune checkpoint.

I think we have seen an incredible efficacy in this patient population.But as you mentioned, it's only a subgroup.It's important to test for it.I know and I'm sure that many of the listeners have heard that there are a lot of efforts to develop immune therapy combinations for patients who do not have this molecular characteristic of MSI high in order to see if immunotherapy can be effective in this patient population, combining with other either immunotherapies or targeted agents in order to see what the effect could be.

DR. GROTHEY:Great, and it's easy to test for.We know we can easily identify these patients who are and who are not candidates for immunotherapy right now with FDA approved agents.

DR. LENZ:I think it's maybe important.Sorry, Axel, but we know these characteristics go along with certain clinical and pathological criteria.These tumors are more likely on the right side.It's usually females.It's patients younger than 50 who have a family history and the histology is usually poorly differentiated or mucinous.There are some hints for the oncologist and the patient to think I have a family history or it's on the right side, I'm very young, even no family history.That should trigger the testing for this particular characteristic because it has a completely different impact on treatment.

DR. GROTHEY:Very good.We're coming to the end of the half hour here.There's one question about ctDNA, so the liquid biopsy again.We talked about the usefulness in early stage to really identify what we call molecular minimal residual disease, persistent cancer in the body.The question is about how it's being used in stage 4 disease.Can we monitor chemotherapy?Can we use it as a tool to make treatment decisions?Dusty, what's your take on that?I know we could probably talk about this for 30 minutes alone, but just a quick two-minute answer.

DR. DEMING:You have to be careful what you get me started on.I think the issue with ctDNA in predicting response to treatments, is for most patients we don't need another tool to predict benefit.Meaning it's pretty easy to use CEA and CT scans for most of our patients and understand whether they're responding or not.In fact, many of my patients have clinical benefit and that is already telling me that they're having easier bowel movements, so I know the treatment's working.

Now there are instances, for example, with immune therapy for MSI high cancers where sometimes the scans aren't as obvious.It would be nice to have a marker that would tell us for immune therapies if patients are responding to those therapies.Because sometimes the CT scans are not as reliable and many of those cancers actually don't have CEA expression.There is literature now using ctDNA assays in that setting, showing the ability to predict response, which I think will probably be something that will be important as the field grows there.

The other instance is looking at changes in the molecular profile of the cancer, especially after targeted therapies.If it was a PAM [phonetic] wall-type tumor that was treated with an EGFR inhibitor, understanding the mechanisms of resistance for that can be helpful in determining other therapies.Additionally in the setting of a HER2 amplification, if using trastuzumab, pertuzumab, those types of therapies, understanding the resistance to that can lead to options both standard of care, but also clinical trials.

DR. GROTHEY:Very good.I'm pretty excited about the immunotherapy, ctDNA technology, application.I think we're just scratching the surface of how oncology is going to change in the next years, and it's great to be in this field.

We are coming to the end.Unfortunately, we are out of time.If you as the audience would like to watch this webinar on-demand, it will be available on Curetoday.com/Webinars within the coming days.Curetoday.com/Webinars.I want to thank our panelists, my friends and colleagues, and the audience for attending and participating in today’s event. I would also like to thank CURE and our partners, Fight CRC and Bayer, for making today’s educational webcast possible. Don’t forget to check your email tomorrow for the survey to be entered to win a gift card, if you stuck around.Thanks to all for joining.We’ll see you next time. Take care and stay safe.Thank you very much.

DR. ENG:Thank you so much.

DR. DEMING:Bye-bye.

DR. LENZ:Bye.Thank you.