Educating Patients and Families on Biomarkers and Treatments

Beth Sandy

Eve, I wanted to talk to you about educating patients and their partners about their biomarkers. How do you define a biomarker for the patient and their family and friends?

Eve Segal

That's such a good question. Our team tries to do a good job of explaining biomarkers, but I think it’s conceptually challenging to understand. I try to tell patients that cancer biomarkers can be genes or proteins that paint a story about your disease. I used to say, "You had a mutation." The reactions I got from patients were shock and surprise. They think, "Am I one of the X-Men?" That might be cool for some people, but it could be really scary for others. So I've been saying, "It's a variant that tells us a story about your cancer and it can help us tell what treatments will be more helpful to you since we have a lot of options these days. And for you, we're testing to see if you carry this kind of gene change or variant. The results will let us know if you're going to respond to a targeted medicine or if you would benefit from another treatment, like immunotherapy."

It opens the door for them to understand that their cancer subtype is going to direct how we treat them. It’s a little bit more personalized. What about you, Beth? How do you broach this subject?

Beth Sandy

I agree with you completely. You don't want to use terminology with patients that's going to be confusing. There are two different ways to go about this. The first way, when I'm talking about the testing, I'll say, "We're going to test for different markers." I don't use the word biomarker. I say, "Different markers that your cancer might have tell us more about how the cancer is growing and how we can treat it." Then, if the biomarker test comes back negative, I'll say, "We didn't find biomarkers so we're going to use our traditional chemotherapy and immunotherapy approaches." It's different when that comes back positive. When that happens, I'll say, "We got this report back and it shows that you have a certain..." I do use the word mutation, but I know variant is out there.

Eve Segal

"Variant" can be confusing.

Beth Sandy

Yes, so is the word mutation, so I don't think either of them are great. Sometimes I'll use the word "characteristic." Something like, "So there's a characteristic about your tumor," if I feel like mutation is a scary word. But a lot of times, I'll just say, "We found a mutation in your cancer cell that is driving the growth of your cancer cell. Therefore, the best way to treat this is to give a medication that is targeted to that driver so that we can target and kill the cancer better, hopefully with less toxicity than our traditional chemotherapy approaches." We try to break it down like that in easier terminology and keeping it as simple as possible is helpful. That leads us to the idea that there are different types of biomarkers; there are driver mutations such as EGFR versus things that are more prognostic, such as PD-L1.

I typically think of EGFR as somewhat prognostic as well because these patients tend to do better because we have targeted therapies that can help them live longer than most of our chemo and immunotherapies traditionally do. I don't necessarily say to them, "You have this prognostic biomarker versus a predictive biomarker." We test all the squamous patients too for PD-L1 expression. Everybody with lung cancer gets that testing, so I'll explain, "We're going to use immunotherapy no matter what unless you have some kind of transplant history or something that makes you contraindicated." But typically, with PD-L1, everybody is going to get some education on that.

And if they come as a low expressor, I'll say, "Well, you have some PD-L1 expression, which predicts that immunotherapy by itself might not be strong enough and we need to add chemotherapy," as opposed to a patient who's a high expressor of PD-L1. To that patient, I explain, "This predicts that you're going to respond better to immunotherapy by itself and we don't have to use chemotherapy up front." This is as opposed to a more diagnostic finding such as EGFR, where I'll say, "Well, we found this driver mutation that..." I don't like to say, "Oh, you're going to live so much longer," because I don't know that that’s 100% true. But I would say something like, "This is something that we can now target and oftentimes there's a chance that you can respond for a long time to this medication, so we won't have to use chemotherapy until later."

Do you get into the nitty-gritty, Eve, when you say this?

Eve Segal

Not necessarily. I feel like PD-L1 as a biomarker is pretty confusing and dynamic. It's not the perfect biomarker, and it can change throughout somebody's disease treatment course. But I think what you alluded to is great because somebody might be looking at their results and say, "I'm a PD-L1 expressor of 42%. What does that mean?" I’ll tell them that it informs the treatment decision. I’ll say, "I'm going to add chemotherapy because you'll have a better outcome versus if you were a high expressor." You can spare them from the chemotherapy side effects. But yes, what you say about the prognostic biomarkers of EGFR or ALK, that really does inform the course. And in the case of ALK, a patient never has to see chemotherapy as a possibility. We have so many oral agents that we can usually spare them from that. We have a lot of targeted agents now for really rare subtypes that are very effective as well, which helps certain patient populations avoid chemotherapy.

Beth Sandy

Do you want to touch on why biomarker testing is important? I don't know that this is a topic that comes up with every patient, but when it does, we tell patients, "Okay, you have stage 4 lung cancer, but we're going to wait a little bit until we treat you." Patients usually respond, "What? You're going to wait to treat me?" That’s when it’s crucial to say, "Well, this is really important because we need to know that we're selecting the proper treatment for you, and we want these results back." And that can be a source of contention. I know if I had lung cancer, I'd want my treatment to start today or tomorrow, but sometimes we need to delay it a bit while we wait for these results. It’s typically not too long, and the delay depends on how symptomatic they are. Does this come up a lot in your practice, patients questioning whether biomarker testing is actually important?

Eve Segal

Yes it does, and I can sympathize. From a patient’s perspective, it's been such a long journey for them to just get here, and they're ready to go. And now you're telling them, "Okay, we're going to wait a couple more weeks." That could be pretty overwhelming and produce a lot of anxiety. But we tell them, "We have just so many effective treatments now for lung cancer, and we can potentially spare you from the side effects of chemotherapy. If your disease is not progressing really rapidly, let's just wait until we get the results." That being said, we have some patients who are pretty symptomatic and have to start on chemotherapy, so we'll convert them over to the more actionable agent if those results come back positive.

Beth Sandy

I think in those young, never-smoking patients, we're a little more likely to wait for the results because those are typically the patients whose treatment is dictated by front-line biomarker testing or biomarker-directed therapy. And that leads me to my next point, that not all these mutations are immediately actionable. Let’s say we wait, and a patient comes back with an EGFR exon 20 insertion, which is uncommon but something that I've seen a fair amount of. This is not something that is approved in that front-line setting. A patient would likely say, "Well, we waited all this time and now I'm still going to get chemotherapy up front."

We have to set expectations that things like EGFR exon 20 insertions, HER2 mutations (not expression like in breast cancer, but a HER2 mutation in lung cancer), and KRAS G12C are all things that we use treatments for in the second-line setting for now and we’ll still give them chemotherapy up front. I don't necessarily say to patients when they're waiting for results, "Hey, this might not be actionable right away." But once those results come back, we’ll say, "Well, we found this, but it's not something that we're going to use until the second-line setting." I don't know how you've approached that conversation in your practice. It can be tricky.

Eve Segal

It can be, and it can be challenging because even though some of our guidelines might say, "This is an emerging biomarker, you can consider treatment with this," but getting a payment for those agents can be challenging because they’re often fairly expensive oral treatments. We do a similar approach to yours as well, saying, "We found something, but it doesn't seem like it's actionable at this time. We're going to proceed with our standard treatment. And then at the time of progression, we'll try this other option."

Beth, let’s take a moment to talk about best practices for addressing equitable care in patients. We need our whole team to understand what resources our patients require.

Beth Sandy

Most of our targeted therapies are oral, and they can have high copays. What one person considers a high copay, someone else might not. A copay of $100 a month can be a lot for our patients, and we may not understand that. I think it’s good to ask a patient if they are having difficulty covering copays and related treatment costs. The majority of drug cost assistance will come from the manufacturer of the actual drug. Other support systems, such as charitable organizations or patient advocacy groups, are available for help related to the treatments, such as travel costs and lodging.

Eve Segal

I agree. We also need to reevaluate our patients regularly. Life circumstances change, especially with the high cost of cancer care.

Beth Sandy

We need to think about specialty pharmacies and where patients live. These medications are not stocked at CVS, Walgreens, or Rite Aid, so this is not a prescription that I can send to them. Patients need access to either a specialty pharmacy or get the medications mailed. I believe when the medication is mailed, the patient often needs to be home to accept the medication. Depending on where the patient lives, it can get very cold. I don’t think a $20,000 medication should be left on the front porch when it's 10 degrees outside. I think where the patient lives needs to be taken into account. Are they able to get these medications shipped to them?

Eve Segal

For patients with language barriers, it can be challenging to call these outside specialty pharmacies to make sure that shipments are set up, especially if there are delays. It’s important that the patients understand the delay and can communicate the delay to the clinical team.

Beth Sandy

That's a good point. You've jogged my memory about a patient who's been on ALK therapy for more than 5 years. For some reason she doesn't answer her phone, so the specialty pharmacy can't get in touch with her half the time. They won't ship the medication until they get in touch with her. Her shipments are often late, and I know there's probably a compliance issue there. But when we see her, we try to educate her, saying, "Make sure you're answering your phone because they need to deliver your medication, which they can’t do unless they speak with you first. Make sure you're going to be there." All these little real-world concerns actually come up.

Eve Segal

Yes, it’s important to pay attention to these things that can make a difference in a patient’s treatment and outcome.