Utilizing Clinical Pathways in the Treatment of Patients With ALK-Positive NSCLC

Tejas Patil, MD, University of Colorado Cancer Center, discusses recent developments in the treatment landscape for patients with ALK-positive NSCLC and how clinical pathways can help standardize the treatment practices for these patients.

Transcript:

Tejas Patil, MD: Hi, my name is Tejas Patil. I'm an Assistant Professor of Thoracic Oncology at the University of Colorado Cancer Center. My main research interests are in patients with oncogene driver mutations in lung cancer, such as ALK, and thinking about novel ways to approach the management of these patients and thinking of new therapeutic options. One thing that's really important for ALK- positive non-small cell lung cancer, and oncogene-driven lung cancer as a whole, is the need to understand acquired resistance, and that's a major research focus of mine.

How are clinical pathways developed and used at your cancer center?

Dr Patil: Clinical pathways can help standardize practice patterns in oncology. In our institution, we have pathways that can help oncologists start patients on a recommended therapy. And specifically when therapies are selected, there's a standardized treatment plan that's placed in the electronic medical record that allows for patients to receive similar doses, similar frequency of visits, that kind of thing. It allows for a patient to receive a relatively uniform experience. And given the complexity of thoracic oncology with multiple biomarkers and different treatment options, pathways can be a way to ensure that patients are receiving NCCN concordant care.

Can you walk us through a hypothetical scenario where a patient is diagnosed with ALK-positive NSCLC? How would you treat this patient? Would they follow a specific pathway for ALK-positive NSCLC treatment or are the pathways further stratified?

Dr Patil: When a patient is newly diagnosed with non-small cell lung cancer, a couple of things need to happen in short order. The patient needs to have a pathologic diagnosis, and in fact, that's happened by them receiving a diagnosis of non-small cell lung cancer. So a pathologist has looked under a microscope, they've used a variety of different immunostains, and classified the cancer as being a cancer that is labeled as non-small cell lung cancer.

However, the work is not done at this point. Patients do need to know the extent of which the cancer is spread, and that requires a variety of different imaging such as PET scans and MRIs. And in the modern era, that also is not enough. We need to molecularly diagnose patients. And so, in addition to getting a tissue diagnosis that says, hey, this cancer came from the lung, we need to have better understanding of the potential molecular targets that could be involved, of which ALK is one of them.

Now, to the question of do we use a specific pathway for ALK? Not directly. What I mean by that is that I don't think that once a patient has a diagnosis of ALK-positive lung cancer, that there's one way to treat them. And in part—we'll talk about this a little later in this talk—there are multiple therapeutic options available for patients with ALK-positive lung cancer and the field has not settled on which is the most optimal therapy for them.

Can you talk a little bit about any recent updates in the ALK-positive non-small cell lung cancer treatment landscape?

Dr Patil: We had talked about this a little bit earlier. Patients with ALK-positive non-small cell lung cancer have a variety of targeted therapies available to them. So these targeted therapies come in the form of small molecule inhibitors. The first drug on the map was crizotinib, which was a very potent ALK inhibitor that was studied in the initial profile 1014 study. But since then, a lot of newer drugs have come into the landscape. These drugs have the added property of having improved brain penetration and [the] drugs include alectinib from the ALEX study [and] brigatinib from the ALTA 1L study. And even more recently, we have ensartinib and lorlatinib. And lorlatinib is of particular interest because of the high intracranial penetration of this drug and this unique side effect profile that we see with this therapy.

New therapeutic approaches can be tricky to incorporate into the current pathway. What level of evidence is required for you to decide that the clinical pathway needs to be updated?

Dr Patil: This is getting at hierarchical levels of evidence that help inform whether we should change pathway decisions. I think the gold standard would be a randomized Phase 3 study that compares one treatment to another. Historically, that has been the gold standard. Practically, why this is a challenge in ALK-positive non-small cell lung cancer is that these patients do really well with these targeted therapies, and Phase 3 studies, especially Phase 3 studies where overall survival is an endpoint, these can be trials that can go on for a very, very long time. And so there's been a lot of interest in using data points that may suggest efficacy at an earlier time point, whether that includes things like objective response rate, PFS, these are all clinical trial metrics that can help separate out different therapies.

One thing that's unique to ALK-positive non-small cell lung cancer that we need to think about is that because these patients can do so well on therapies and have a long period of time before any progression event, it's really important that quality of life indices are incorporated into the discussion. Many of these patients will be on their drug for years, and side effects actually might wind up playing an important role in differentiating which treatment should be preferred over another. And that's something that hasn't been historically considered, but may be something that needs to be revisited for patients who have ALK-positive non-small cell lung cancer as their management is starting to look, in some ways, much more like chronic myelogenous leukemia or CML.

One of the challenges of using clinical pathways is the struggle between standardizing treatment decisions across the patient population and optimizing care for individual patients. How do you balance these priorities in a disease like ALK-positive non-small cell lung cancer?

Dr Patil: This is always a challenge, and while I see a value in standardizing treatment decisions so that as an aggregate whole a population benefits from standardized harmonious goal concordant care, I think we all know this, patients are different, people are different, and every clinical situation is unique.

When I think about a patient with ALK-positive non-small cell lung cancer, I know two things. One, this is a rare population, and two, the management of patients with ALK-positive non-small cell lung cancer is very different than lung cancer generally. And it goes to the fact that these patients, generally speaking, have a really robust response to their targeted therapies.

And so when clinical situations come up where, for example, if a patient is progressing on their ALK-positive non-cell small lung cancer, my first question would be, well, are they progressing in multiple areas or is it maybe just one area in the lung that's progressing? Can we use multimodal therapy to allow them to stay on their drug but just deal with potentially problematic areas one at a time? That is a newer thought pattern and paradigm in non-small cell lung cancer. But in the ALK-positive world, I think individualizing treatment is really important. These are patients that have very unique biologies and their problems are going to be slightly different than a patient who's receiving an immune checkpoint inhibitor, for example.

What are some other challenges that you face in optimizing decision making in your practice?

Dr Patil: The first challenge I see is that there is a lack of transparency and some opaqueness into the actual financial costs of these drugs. And having that front and center can actually be very important in helping design a pathway. So financial toxicity is a term that's been thrown around a lot, but is very important for patients.

I think another challenge has been the lack of really good real-world data regarding chronic adverse events. As I mentioned, patients with ALK-positive non-small cell lung cancer live for a very long time and have to endure the effects of their therapies. We have very little data on real-world adverse events in patients who are receiving these, and I think having that information could actually be very helpful in stratifying treatments.

And the third challenge is that ALK-positive non-small cell lung cancer has some unique issues when it comes to resistance. And some of the challenges I've had is when we identify a resistance mechanism in patients who are progressing on their therapies, it can be very hard sometimes to convince payers or insurers that combination treatments, that is patients remain on their ALK inhibitor and we're going to add in a new treatment, is financially justifiable. Even though there is emerging data to suggest that this may actually be a useful approach, I think that the field as a whole is still understanding how to best do this.