Advances in Testing and Targeted Therapy for NSCLC: Translating Evidence to Clinical Practice - Episode 2
A brief review of real-world data behind molecular profiling in non–small cell lung cancer, followed by a discussion on barriers to testing and uptake.
Benjamin Levy, MD: Let's talk about that journey and the challenges of that journey. We all think we're involved in best practices and that all of our institutions get 100% results in all of our patients. We know that's not true in the real world. Alex, you were involved in some of the real-world data looking at next-generation sequencing. How it's done in the community, and what percentage of patients are actually getting this? This was presented last year at the 2021 ASCO [American Society of Clinical Oncology] Annual Meeting. It was from the US Oncology Network. You were part of this. Can you walk us through some of that?
Alexander Spira, MD: Essentially, what they did was they looked back. Now it is a few years old, of course, but they went back and looked at the rates of testing of multiple different biomarkers. The first 1 and the most common 1 is EGFR. EGFR has been around as long as I've been a medical oncologist. I know I'm dating myself. Even in this day and age, at its peak, it was still only about 70% to 75% of adenocarcinomas getting EGFR. Remember the story's not old. This isn’t an old story. The fact that we're still not testing—when in the breast cancer world, everyone gets tested for ER [estrogen receptor] and PR [progesterone receptor]. They would gasp at this. Then when you took another step back and you went to ALK or ROS, never mind RET and BRAF, it was down in the 40% to 50% range. Some of that, of course, is tissue quantity. Some of it's a little bit dated, but the reality is that it needs to be better. That's the challenge that we're living in right now and it's obviously affecting patient care. It was a little bit embarrassing when this data comes out because you're part of it and like here's what we're doing and we're not really doing a very good job, but thankfully we raised a lot of eyebrows and said, “We all need to be doing a better job.”
Benjamin Levy, MD: I just want to mention some of the data in line with some of your experience at US Oncology, there will be a poster presented on Monday at ASCO looking at CancerLinQ data with roughly 37,000 patients, the NGS [next-generation sequencing] completion rate was not that good. It was around 50%, so you're not the only one. There are other data sets that would suggest the same thing. We're going to have another poster on Monday by Dr [Madeline] Hooper et al about reflex testing vs not reflex testing. Do you want to walk us through that, Alex, just briefly?
Alexander Spira, MD: It's the AmeriPath group, Quest Diagnostics. They basically went back and looked at 2 different time periods, so you have to take that with a grain of salt. The 2 time periods were before reflex testing was instituted and after reflex testing was instituted. In essence, the turnaround time was 35 days versus 18 days.
Benjamin Levy, MD: Not surprising.
Alexander Spira, MD: That's huge. That's twice as long. It's not just the time. There are patients waiting to get treatment or maybe not waiting to get treatment, and maybe getting the wrong treatment as well. There was also a huge number of patients that would've had their treatment changed and a lot more patients were even found with biomarkers when they went back and looked versus not. This raises a lot of eyebrows, should it be reflex tested or not? You probably should.
Benjamin Levy, MD: We have challenges at my institution instituting reflex testing. We've had a rule that the pathologist can no longer be the ordering physician for next-generation sequencing. That leaves it up to the medical oncologist, the surgeon, the interventional pulmonologist, or these through an epic function. It's a real challenge. I'd like to hear from everyone here. Just what are the greatest barriers? We mentioned the tissue journey and it even starts with some sort of communication about how tissue's going to be procured. Jonathan, what do you see as the biggest barrier to this? We've seen this real-world data come out over and over again that we're just not doing a great job. What do you think is the biggest challenge in biomarker testing for lung cancer?
Jonathan Wesley Riess, MD: I think some challenges are just the logistics of that [tissue] journey: getting the tissue, the order, the pathologist cutting the slides, and then getting it sent out. Sometimes there are some insurance issues. Those things can lead to a substantial delay, which is why I find myself sending off both tissue and plasma more and more when I initially see patients. We're working with our pulmonologists and other in-services and so forth to get tissue and plasma done as early as possible, because it really can be very informative in terms of getting that early data. It's very gratifying to get an EGFR or ALK or 1 of these oncogene driver positives within a few days of seeing a patient and already have that data when you see the patient. It really accelerates getting patients onto the most appropriate treatment and not missing those game-changer mutations.
Benjamin Levy, MD:Chaitali, any other thoughts on the challenges of tissue biopsies at your institution? Is it tissue procurement? Is it not enough tissue that you're not getting? What do you see as the biggest challenge at your institution?
Chaitali Nangia, MD: I think the first challenge I see because we do get a lot of referrals from the community as well as, is who's going to request the test. Who's going to be the guardian of requesting the test. I think half the time is wasted right there because they don't necessarily get to see medical oncologists right off the bat, but everybody's nervous ordering, including pathologists. They want to know what tissue you want to be sent out. You may have mixed histology, so that makes a difference. They want the medical oncology input and it takes a while before they even get to a medical oncologist. I think insurance is also a big player in this. There are some very restrictive medical groups. They will not let you do an extended panel, or they limit you by doing just PD-1 testing and nothing else.
Jonathan Wesley Riess, MD: I would just like to amplify that. That's becoming more and more of a challenge for the earlier stages where you have the ADAURA data. Sure, there's a single test for EGFR that would be a PCR test, for example, that would be available. But as mentioned before, you really want to know those ALKs and ROS1s—not only for studies and potential future treatment—but also now with immunotherapy coming to the fore, they may not be the right patients for adjuvant or neoadjuvant immunotherapy.
Benjamin Levy, MD: Any other comments on challenges of tissue?
Alexander Spira, MD: It is kind of ironic. These tests are expensive. They're not cheap, but when you think about how much we spend on lung cancer patients per month, we're talking about a couple of thousand dollars, maybe even less for some of this testing, but the cost of immunotherapy for a month is $15,000. When you talk about the marginal cost to get all the information, it makes no sense whatsoever that that should even come into play.
Chaitali Nangia, MD: I think another thing I would like to say is the adequacy of the tissue sample. That also plays a big part. Sometimes you go through this whole exercise just to wait 2 to 3 weeks only to find out that it was an inadequate sample. That's why I'll end up doing the plasma as well, because I can’t be sure that I'm going to get the results back, or they may end up doing the whole process and say, well, I can only report you one. Which one would you like to know?
Alexander Spira, MD: That's actually going to become even more important. We will talk more about neoadjuvant stuff and neoadjuvant protocols. You get chemo-IO [chemotherapy plus immunotherapy], but what do you do? You need all that information.
Benjamin Levy, MD: I would bookmark this because I want to ask everyone again about the data coming out with neoadjuvant—chemo-IO, getting the results, and then EGFR and ALK results before you pull a lever on neoadjuvant chemotherapy. That's tough, and how that patient went on, we'll talk about. Do you have any other comments on tissue stewardship, Heather?
Heather Wakelee, MD: I think that patients who come in and get admitted in the hospital and are diagnosed at that point, that that's even harder, because I don't really have anyone who feels like this is my patient. “This is a patient who is mine while I'm in the hospital for today's shift.” That becomes a problem. Then there are reimbursement issues around that that are even bigger than what we've talked about before. I think these are real challenges, also.
Jonathan Wesley Riess, MD: That's a great point. I would just highlight that. It's really important. We have patients that get admitted to the hospital that really need to be treated, and being able to get timely biomarker testing can be critical. I just got paged the other day. We sent off plasma, and it came back ROS1, and the patient is in the ICU [intensive care unit] getting crizotinib through a feeding tube. Testing can make a huge difference.
Benjamin Levy, MD: Not wrong to do. Absolutely. Jessica, you've been waiting patiently here.
Jessica Donington, MD: I was just going to say the entire inpatient reimbursement thing affects all the surgical patients because they're all inpatients and none of it is reimbursed while they're in the hospital. So they all have to go home. They all have to wait 14 days, and then someone has to remember to order it. Just adding that delay and that extra step is just asking for it to fall through the crack.
Alexander Spira, MD: All I will say, though, is I know this is much more expensive and much more complicated than IHC [immunohistochemistry] standing, but in the breast cancer world, a breast cancer patient might have 5 biopsies and they're all checked for ER, PR, and HER2 [human epidermal growth factor receptor 2]. It shouldn't be this complicated.
Benjamin Levy, MD: There's no excuse, really. We have too many good therapies that we can now give even to ICU [intensive care unit] patients and turn them around. It's inexcusable that we're still currently at the rate that we are. One of the other things is that we published a paper maybe 10 years ago—just best recommendations for molecular testing. I think having a physician-champion—somebody in the health system that can marshal this through, specifically in the community—makes a lot of sense. There are so many hurdles along the way, as we've mentioned with this tissue journey from procurement, as Chaitali mentioned, all the way to the result. Getting the result and then interpreting the result—there are educational needs there, too, with some of these rare mutations. I hope if we meet in another 3 or 4 years, we can talk about better percentages for our patients in the completion of NGS.
Transcript edited for clarity.