In this journal section, we speak with cancer care practitioners about their clinical pathways and pathways programs being used in their practice, including how they are being applied in a particular disease state and what challenges persist regarding treatment decision-making and personalized medicine integration.
In this “Pathways in Practice” installment, we spoke with Mark A Socinski, MD, executive medical director, AdventHealth Cancer Institute, about their pathway for non-small cell lung cancer (NSCLC). Dr Socinski is a board-certified, fellowship-trained medical oncologist, specializing in all thoracic malignancies, including small cell and NSCLC and mesothelioma. He is an internationally recognized expert in the development of novel chemotherapy agents and treatment strategies for advanced NSCLC and small cell lung cancer. His research has focused on incorporating personalized medicine and molecular biomarkers in the treatment of lung cancer.
Does the NSCLC clinical pathway used across the AdventHealth Network include tumor agnostic tests and, if so, where in the treatment pathway are the tests located?
Dr Socinski: The pathway we use—formerly Via, now the Elsevier ClinicalPath—is divided by disease sites. For instance, in the lung cancer pathway, we ask if the patient has an NTRK fusion. Obviously the two TRK inhibitors, larotrectinib and entrectinib, are not tumor specific, they are tumor agnostic. They are specific for an NTRK fusion, which is why we ask that particular question in the lung cancer pathway.
Now, only a small percentage of lung cancer patients will be found to have an NTRK fusion. So, it will not be a very common finding, but we think it is an important finding because of the significant efficacy of both entrectinib as well as larotrectinib in that setting.
If you are navigating a patient through the lung cancer pathway, the pathway will prompt you: “Does the patient have small cell or non-small cell lung cancer?” If you say non small cell, then it will ask you questions about the stage and performance status of the patient. If it is the appropriate stage, which is stage IV, and the histology is nonsquamous, then it will ask you not only about NTRK, but it will ask you four or five other things like EGFR mutation, ALK translocation, ROS1 translocation, and BRAF mutation. It also asks programmed death-ligand 1 (PDL1) status.
It also has a category for other actionable mutations since you might have say a MET or RET alteration or some other alteration in which there might be a targeted agent. Capmatinib and LOXO-292 were just recently approved by the Food and Drug Administration for MET and RET respectively.
The pathway gives the advantage to the patient by prompting that the physician should at least be thinking about these sorts of other things.
As the co-Chair of the committee for the NSCLC pathway development for Elsevier’s ClinicalPath, could you speak to the level of evidence that the committee considers appropriate for including any agnostic test on this pathway?
Dr Socinski: I think that we all recognize that cancer is a disease of your DNA. The standard of care in many clinical situations is to interrogate the patient’s DNA to see if there is an actionable DNA alteration. If you have one of these DNA alterations, then in many cases it is paired with the targeted therapy. There is broad acceptance of this practice among people who do frequent molecular testing.
If you have a known driver alteration, for example, if you have a RET fusion or RET mutations, whether one of those is in a lung cancer patient or a thyroid cancer patient, the implication is that this is a driver. If you target the driver, then you have a much greater response rate than you would expect from chemotherapy.
NTRK is another great example. You know NTRK occurs across a broad range of tumors, but all the activity with the TRK inhibitors suggests that you have the same level of activity across all of these tumors because this is a driver.
Another indication that we have that is tumor agnostic is microsatellite instability-high (MSI-H). Again, if you have MSI high, it does not really matter what type of tumor you have; the response to immunotherapy is significant and you want to get that treatment to that patient given that molecular finding, agnostic to the anatomic site or agnostic to the histologic morphology that you may see under the microscope.
Are the payers that AdventHealth is contracting with generally receptive to covering these tests? What efforts are underway to work with payers to make sure that they are on board with including any of these tests in the regular treatment protocol?
Dr Socinski: It is variable. In a perfect world in lung cancer—I would argue this is probably true in any cancer—you should do the molecular testing that is appropriate. If you find a molecular alteration that is associated with a targeted therapy, that is what you should do, because in those situations the targeted therapy has been shown in certain cases to be far superior to chemotherapy.
The results that we see with a true oncogenic driver with targeted therapy far exceed what you expect either with chemotherapy or immunotherapy, so they should get a targeted therapy. If they do not have a target on comprehensive genomic testing, then you need to consider PDL1 and other issues in terms of how to treat the patient.
Now, most of the time in my experience, the third-party payers have not necessarily been thinking in that manner. The chances are that you are not going to find anything with molecular testing. There is an 80% chance that the patient will need chemoimmunotherapy. However, a patient I saw in February 2020 had insurance that said we need to do the molecular testing, which takes a week or two. When we requested prior authorization, they pushed back and said, “What are the results of her molecular testing?” I was actually surprised and impressed at that response. Then they asked, “What was her PDL1 status?” The insurance company’s rationale for that was “We are happy to pay for treatment, we just want to make sure we are paying for the right treatment,” which I had not encountered before this case.
That is my anecdotal experience. Now, if I were running an insurance company, that is exactly what I would do. Tell me the results of comprehensive molecular testing, tell me the PDL1 results. Let us agree that the evidence supports that this is the best treatment for this patient and that is what we will reimburse.
As more mutations or targeted drivers continue to emerge across all sorts of different solid tumors, what efforts are underway to stay abreast of incorporating the latest agnostic tests in the regular treatment of your patients with NSCLC?
Dr Socinski: Well, I am solely focused on lung cancer; I obviously have a leg up on most community oncologists because they are doing general oncology and seeing many different cases and different types of cancers, which I do not have the burden to have to deal with.
In my case, it is what I specialize in for a living. I think from the community oncologist standpoint, it is a real challenge to keep up with all of the information that is out there on all different tumors because of the rapid developments—not only understanding the biology of all these cancers, but also with regard to new therapeutics.
I have lost count of how many new drugs the FDA has approved over the past several years in oncology. I have heard a recent figure that 40% of the drugs that are currently under consideration by the FDA are actually cancer drugs. It is pretty overwhelmingly mind-boggling to me that we have all these new drugs coming to market that need to be used in a specific circumstance for which they were developed and are FDA approved. Staying abreast of all that can be challenging if you are doing all different tumor types.
I am biased to the idea that the clinical pathway helps in this regard, assuming that the pathway is developed and frequently updated by experts in the field. If you are using high-quality pathways like that, then you can rely on that pathway to get the right treatment to the right patient at the right time, whether it is specific for that tumor type or it is tumor agnostic in the case of NTRK.
Pathways can be a failsafe mechanism for holding your physicians to a defined standard of care for a particular patient.
