In this journal section, we speak with cancer care practitioners about their clinical pathways and pathways programs being used in their practice, 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 speak with Mark A Socinski, MD, about the development of AdventHealth’s lung cancer clinical pathways. Dr Socinski is a board-certified, fellowship-trained medical oncologist, specializing in all thoracic malignancies, including small cell and non-small cell lung cancers (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.
In your own words, how would you define a clinical pathway, and how does AdventHealth define a pathway program?
Let me first set the stage with a bit of context—we are talking about oncology care, where in the past 3 to 4 years the Food and Drug Administration (FDA) has approved 30 to 40+ new drugs for many different indications. The treatment arena has become very complex, and there are always issues about efficacy, toxicity and, of course, the issue of costs. I think there is a great deal of variability in how oncology is practiced in terms of what oncologists do in different situations—obviously never intentionally ill-guided. But with the amount of information we have, the amount of new indications and the various types of patients that are diagnosed with cancer, there ends up being a great deal of variability in treatment, and variability brings with it inconsistencies, cost issues, etc.
So having said all that, my definition of a pathway is a process that tries to make sure that every oncology patient gets the right treatments at the right time for their stage of disease and the characteristics of their disease. A pathway drives you to as close as you can get to a single choice. But medicine is not a perfect science, and sometimes there is more than one choice. Then is it up to the provider to distinguish the proper choice for the patient.
A pathway is a tool that takes the most current medical evidence and synthesizes it into a treatment paradigm that aims to embody the best standard of care, ultimately aiming to reduce variability in care. If your pathway is making sure that patients get the most efficacious therapy possible, the most cost-effective therapy, that is going to result in better and higher value health care.
With that explanation in mind, is that how AdventHealth organizes their pathway programs? Could you also walk us through the process of pathway development or pathway updating at AdventHealth?
Yes, I would say that is an accurate depiction of how we think about pathways. From an oncology point of view, there is a spectrum of pathways, some internal and some external pathways. We do use Via Pathways, at least for our medical oncologists. Via was a product of the University of Pittsburgh, UPMC. It started around 2005, commercialized in 2009. I became part of the lung cancer committee as a co-chair in 2011. The philosophy of Via is that you can drive the treatment decisions to a single choice 80% of the time and that that choice should be determined based upon first, efficacy—we want patients to be given the best treatment for their cancer. Secondly, toxicity—we don’t want undue toxicity, although obviously, we expect some. And then the third is cost. Via does have a cost analyzer that can give information about the issue of cost.
Via is made up of disease-specific committees. The committees have co-chairs who are typically academic, but some of them are community oncologists. Most of the committees get together on a quarterly basis. For instance, before the quarterly teleconference lung cancer call, me and my co-chair at City of Hope meet with the Via support staff and create an agenda. The agenda may include, for instance, the consideration of a new drug or a drug with a new indication in lung cancer; we have to figure out if that is going to be incorporated into the pathway, and where in the pathway should it be incorporated.
Another issue we may consider on these quarterly calls is that the pathways are very fluid organisms, if you will. They need constant revising and perfecting. We constantly are discovering knowledge or new evidence that means a pathway needs to be tweaked a little bit. And so, sometimes the pathway agenda is focused on looking at the current status of the pathway and saying, we need to make some decisions about this particular choice in the pathway, and that’s usually based on some new data or observations.
Now, I will say that even though we have quarterly meetings, occasionally, there is something that’s so important that it needs addressed immediately. For instance, a couple years ago when osimertinib was approved in T790M-positive EGFR mutations, we thought that that couldn’t wait for a quarterly meeting. So, within one week of the FDA approval, we convened an ad hoc committee and had the discussion about (1) should this be in the pathway, and (2) where should it be in the pathway. We felt that it was important to call an ad hoc meeting for something like this.
And at these quarterly meetings, can you explain how the group reaches consensus?
The co-chairs run the meetings along with the Via support team. We have a PharmD at Via that works in the lung committee structure. We have a presentation of the data, then we have a discussion. The committee members can voice any opinions or concerns they have. There is often a robust discussion, and multiple viewpoints about the question under consideration are debated.
At some point we have to make a decision about framing the question or framing the statement. A few years ago Via implemented a voting process, so they could document the decision of the committee in a democratic way.
The other very important thing the Via process does is to document why the pathway choice was chosen. Was it based on efficacy, toxicity or costs? The process of documenting the discussion followed by a committee vote and documenting the reason for the pathway change creates an objective record of the committee deliberations.
Could we dive a little deeper into the pathway that AdventHealth uses for NSCLC? Specifically, what is the approach to stratifying patients with NSCLC to help guide therapeutic decision making?
In NSCLC, as you maneuver the pathway, you are asked first about stage and asked to record the TNM stage (ie, tumor, nodes, metastases) of the patient. Then you’re asked to document the histology, whether it’s squamous or non-squamous. Then you document the performance status on the ECOG scale. If it’s a non-squamous, you’re asked to document the molecular testing profile, EGFR mutations, ALK and ROS1 translocations, BRAF mutations, so on and so forth—all the National Comprehensive Cancer Network (NCCN) things. The pathway does ask for other actionable mutations such as RET fusions, for example. We also ask for the PD-L1 status of the patient. This information is critical to the management of stage IV disease. As you can see, we do a pretty comprehensive profile given what the treatment landscape is in 2019.
Could you discuss the benefits of, and maybe a few examples of, adjuvant therapies in this patient population? What is the role of adjuvant therapy within the pathway?
Yes, adjuvant therapy is considered a standard of care for node-positive patients. If you have a resected stage T2N1, stage II patient, it would direct you to an adjuvant therapy choice. The choice of adjuvant therapy differs if you have squamous vs non-squamous disease, so it will direct you to a different treatment. If you opt not to give adjuvant therapy, it will ask you why, and there are a number of reasons why you might not recommend adjuvant therapy in a given patient.
It gets a little more difficult in node-negative patients. If you don’t have nodal involvement, treatment is relatively controversial in this setting. We generally revert to tumor size, and the bigger the tumor, the more likely we are to endorse adjuvant chemotherapy. In the non-squamous population, we recommend cisplatin plus pemetrexed. In the squamous, again, it’s either cisplatin with docetaxel or gemcitabine depending on toxicity concerns.
We do allow in the pathway different choices based on toxicity profiles. A good example is the choice between docetaxel and gemcitabine paired with cisplatin in the adjuvant treatment of a patient with resected squamous carcinoma. Many patients don’t want to lose their hair, and you’re more likely to have hair loss with docetaxel than you are with gemcitabine. The pathway allows these decisions to be made based on patient preferences and the known toxicity profiles of the standard regimens we use in this setting.
We have similar options and branches for other drugs like pemetrexed, for instance. The pathway for pemetrexed says don’t give it to patients whose creatinine clearance is below 45. And there are a lot of patients whose creatinine clearance may be 35 in which pemetrexed is not particularly a good idea. So, it directs you, in this case, to use a taxane-based therapy. The pathway has the flexibility to customize choices based on the details of the patient.
How do you balance the effort at standardization of treatment decisions with the need to optimize care for individual patients on a personal level?
That’s a good question. It gets back to the philosophy that, with the amount of evidence we have, reasonable physicians should be able to agree on a reasonable standard of care most of the time—which happens to be the philosophy of Via as well. Whether most of the time is 80% or 70%, you can argue. We typically use 80%—in other words the standard of care defined on the pathway will be the most appropriate therapy for 80% of patients. We realize that every patient isn’t a round peg that goes in a round hole. There will always be unique situations and unique patient characteristics or preferences. That is why there is no expectation that physicians will adhere to the pathway recommendations 100% of the time—the expectation is that it should be more like 80% of the time, as mentioned above.
Using a pathways approach provides more helpful direction and best practice recommendations than say a guideline approach. For example, if you are only using the NCCN guidelines, the guideline provides you with all possible options, which is many. You may have 12 choices. Well, how do you decide between 12 different things? Guidelines don’t give the physician any direction based on what the experts think is the best thing to do. So, there’s a big difference between a guideline and a pathway.
What are the more challenging aspects of treating NSCLC that make some treatment or pathway choices difficult? In other words, what are some challenges to optimizing therapeutic decision-making that you continue to see in your practice?
As I briefly mentioned earlier, it is getting the right treatment to the right patient at the right time at the right cost. Many treatments work very well in some patients but do not seem to work in many other patients. The issue is, how do you find the patient in which the treatment works well in so you can use it, and how do you not waste your time with patients that aren’t going to get benefit from that treament and need something different. And that’s the whole issue with the term “personalized medicine.” We do personalize treatment to a certain extent in lung cancer, but we don’t do it for every patient. And the tools that we use to personalize the therapy are many times imperfect. We are immensely better than when I started in this business many years ago, but there’s still a need to refine the treatment a bit more to, again, get the right patient the right treatment at the right time—and I would add at the right cost. So, I think that that’s kind of the biggest challenge.
