Rare Disease Report

Exploring Treatment Challenges for Merkel Cell Carcinoma & Other Rare Cancers

JUNE 21, 2018
Krista Rossi
Although skin cancer is the most common cancer in the United States, Merkel cell carcinoma (MCC) is rare; the American Cancer Society estimates that only about 1,500 cases are diagnosed annually in the United States.

At the American Society of Clinical Oncology (ASCO) 2018 annual meeting in Chicago, Rare Disease Report® sat down and spoke with Nicholas J Robert, MD, medical director of Health Economic and Research Outcomes/Health Informatics for McKesson Specialty Health to discuss treatments challenges associated with rare cancers like MCC and recent advances that have been made in this area.

Rare Disease Report® (RDR®): What are the biggest challenges to treating Merkel cell carcinoma? What are the current strategies being used by providers?

Robert: Merkel cell tumor is an uncommon skin tumor; it can become metastatic, and the treatment for it is not very good. As in many tumors today, there is an increasing role for the use of immune therapy.

The issue is, how do you ask the question of is there a benefit to giving immunotherapy to a tumor that’s pretty rare, metastatic Merkle cell tumor. The companies that were developing and manufacturing this approach, EMD Serono and Pfizer, realized [it] would take a long time to accumulate [the number of] patients [for a] randomized trial.

Consequently, a strategy that’s being used now more and more for rare tumors is to treat the patients one way, see what their outcomes are, and then compare this to the data you can find from patients that have been treated; that experience is captured by electronic medical records.

Our role working with this approach was the trial that was done by the company; they obtained certain results, certain end points. We found a group of patients using our electronic medical record called iKnowMed, which is an oncology-specific EMR.

With it, we’re able to identify patients with a metastatic Merkle cell tumor, we’re able to identify patients that were comparable with the patients that were treated on this clinical trial, and we were able to identify the endpoints, including actually measuring the tumors of response using scan reports. This information was used in their application to the US Food and Drug Administration (FDA) to obtain approval.

We’re able to show that we have quality data that was sufficient to this company to assist in obtaining approval for their agent. 

RDR®: While studies in metastatic breast cancer have assessed multi-omic profiling (MoP), did this study utilize this genomic and proteomic profiling that includes exome sequencing, RNA-Seq, IHC, and quantitative phosphoprotein-based protein pathway activation mapping?

Robert: No, but you’re asking a question that’s pressing. We’re finding, and we hope, that maybe we can use biomarkers to better delineate different types of tumors even though they may be under the same name, like breast cancer or Merkle cell. The reality is, there probably is some heterogeneity around those tumor types, and by looking at biomarkers, we can hopefully divide it up into different subsets.

For example, not everybody with breast cancer develops metastatic breast cancer not everybody with Merkle cell develops metastatic disease. Are there different types of tumors you can predict before they become metastatic and then identify those tumors and treat them before they become metastatic?

That’s a general approach in oncology that has potential for application, and it’s an area that’s a very exciting one and very busy with a lot of people involved. It’s called precision medicine, and a lot of it is based on different biomarkers. However, there is a large area, a significant area, something called next generation sequencing where we look for mutations of genes that help us predict outcome.

There is already some progress in next generation sequencing looking at some mutations for rare cancers. I think at this point it’s a bit early to say it can translate into different treatments and different outcomes, but it is a scenario that certainly is exciting in terms of exploration.

RDR®: Could multi-omic profiling be applied to treating other rare cancers?  

Robert: Multi-omni profile is basically looking at biomarkers in different ways. We’re looking to RNA, DNA, proteins, and phosphorylated proteins. Basically, we’re getting a panel of different biomarkers, and the hope is that we’ll see patterns that will help us with prognosis, but more importantly, predict who will then benefit from treatment.

However, 1 of the challenges is that there’s 2 settings when you treat patients with cancer. There’s a setting where the patient has been treated, the cancer’s been removed, but there’s a risk of recurrence. If you treat in that situation, you really have no evidence whether it’s working or not unless you follow patients—which may be months or years—and see their outcomes. The other situation is where you have someone who has metastatic cancer and you can monitor their outcome.

In both situations, one could make an argument that if you could find some predictive biomarkers early on, you could see whether your treatment would help those patients in the interim setting where you can’t really see anything. It’s a black box sort of operation, and in the metastatic setting, you could identify, hopefully, drugs that could work and drugs that don’t work.

You could also do it prospectively, ahead of time, and not treat the patient to find out but use these predictive markers. It’s sort of the holy grail in terms of what we would like to do, I think. We’re far from doing it in most tumors, but it’s where a lot of energy is being expended in terms of research efforts.

RDR®: What do you think are the biggest challenges in creating treatments for rare cancers like Merkel cell carcinoma?

Robert: The biggest challenge is really curing those patients. The window of opportunity in cancer is usually early, where you can do something definitive and remove the tumor and make the patient cancer-free. Once the cancer becomes metastatic, it becomes a challenge because what happens is, it changes its appearance in terms of how it looks on a chemical level and on a gene level and getting ahead of that is hard.

In the past, efforts have been developed in targeted therapies around the pathway that may be altered that’s leading to the growth of the tumor. Immunotherapy is a little bit more agnostic to these pathways (i.e. basically, it’s turning on the immune system to kill out the bad cells regardless of how those cells become bad) and we’re seeing some impact in some tumors.

We’re seeing some benefit but not necessarily long-term, and I don’t think we can use the word cure often in any of these settings. However, this whole strategy is being amplified, and right now we usually give one immune therapy agent [but] we’re learning that maybe giving more than 1 immune therapy agent may be beneficial. We are [also] exploring using other immune therapy agents with other agents. The hope is a combination of those strategies will lead to a positive outcome, at the very least a prolonged benefit, and maybe cure.

There are multiple immunotherapy agents available today. I think an uncommon decision was made to go after a metastatic Merkle cell cancer. By using a combination of their trial and real-world evidence, there was enough evidence to be convincing to lead to approval. The expectation is there will be more immunotherapy agents addressing this issue, addressing this kind of cancer.

RDR®: Where do you see gaps in treating rare cancers, and how do you think these gaps can be filled?

Robert: In the past, it was a real challenge if you had an uncommon cancer to make any progress and do research, and even common cancers that fell into uncommon subtypes.

As we learn more about the different cancers, we’re really finding that metastatic breast cancers have many cancers, and metastatic lung cancers have many cancers. As we become more refined and sophisticated in our understanding of cancer, these subtypes become smaller and smaller, and the issue becomes how to demonstrate benefit.

The traditional approach that we’ve used for a few decades is to do large trials with hundreds and hundreds of patients. They take time, often years, to get results.

The hope is that combining a very well-designed study and comparing it to what’s called synthetic controls developed from EMR data, we can shorten that time if the data is credible and the key is good EMR data, Now, with more and more data being captured in EMR, as the EMRs get better in what we call structured fields, it’s easier to explore that data and find that synthetic control for this approach.

RDR®: What are the most exciting innovations on the horizon for cancers?

Robert: You have to understand that in the oncology world, many of us are pretty optimistic as a group. Thinking about taking care of patients and knowing some will die, you have to be pretty optimistic that improvement is around the corner.

There are many different approaches, from maybe screening earlier and finding cancers before they become metastatic and can be fatal to figuring [out] better ways to treat patients with less toxicity. There are a number of different strategies.

I think right now, the buzz in the oncology community is personalized health care precision medicine. Understanding that there are different types of cancers even within the same name, breast cancer for example, and understanding that better is big.

Let me also make a point that there’s some changes on how we do our work every day. I mentioned electronic medical health records, and we have an EMR that’s designed solely for oncology outpatient care. What we’re doing with that platform is we’ve added another platform, another layer, which helps the physician determine an appropriate treatment.

When the patient is seen using this EMR, the physician is queried for certain biomarkers, and depending on this biomarker result, different treatments are recommended. This helps assist the physician along the way to make that decision, and I think that’s an improvement that’s giving everyone a better chance of good care everywhere, including the community setting.

RDR®: What are some education tools you don’t have but wish you did?

Robert: Probably the most important educational tool that we don’t have, which we should have, is what’s going on with the patient and getting an education from our patients.

The normal routine is we see the patient in follow-up, we spend a few minutes with them, we ask how they’re doing, we usually spend a few more minutes with them, and they spend a few more minutes with the team, such as 1 of our nurses or nurse advocators.

One of the things that’s becoming clearer is we need to have a better connection with our patients to have a better opportunity for our patient to educate us about how they’re doing. There’s something called patient reported outcomes (PRO). They’ve been around for a while, and in the past, it has been pretty clunky; it has been paper driven, but now there are apps that are being developed.

There’s an opportunity for patients to use these apps when they’re at home and not feeling well. They can go onto their apps and point that out. Instead of calling the doctor’s office, they can send that information to the practice where they’re able to receive that information and respond back.

I think there has been an emphasis [on] educating patients in terms of cancer care and an emphasis on the health team in terms of different treatments. However, I think the back-and-forth, the communications with our patients, the education [of providers] is critical, and I think we’re now developing some tools where we have a better opportunity to do that. There’s data to support that it translates to better care.         

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