The Value and Opportunity in Individualized Cancer Care: Part 1

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Oncology Innovations, hosted by Gordon Kuntz, features candid discussions with innovators aiming to advance quality and value throughout the cancer care ecosystem.

Gordon Kuntz: To start off, take a couple minutes and share a bit about the work you’re doing now as it relates to personalized medicine in cancer care.

Bryan Loy, MD, MBA: When you say “personalized medicine” it means a lot of things to a lot of people. If you go to the National Cancer Institute website, for example, you’ll get a definition that feels like it’s largely around molecular testing and tumor biology, whereas if you go to some of the professional organizations, you’ll get learning about the whole patient, what their patients’ values are, and individualizing treatment to align with your values.

I work with Humana and have 20-plus years in the payer business. When you’re managing populations, you get the luxury of doing a little bit of both, working down at the micro level around the testing and also thinking about what we can do as a health plan to improve the member journey.

In a normal health plan—I’ll call it operations—there are functions like pharmacy and therapeutics, where we write policy that are informed by personalized testing and medicine decisions. There are policies that are developed in the medical side of the house, where we look at new technologies for testing, biomarkers, and next-generation sequencing molecular panels, for example, that inform many of those medical decisions that would help one to personalize and craft a medical management path forward that’s specific to the patient.

I spend a lot of my time in oncology, but I also would say I live with both definitions. I, too, am interested in using that type of information and technology to improve upon the member experience. Even though we manage populations, we’re interested in the deliverers of care, or our collaborators, vendor partnerships, and many of our clinical programs, getting to know our patients and making sure whatever technologies we’re bringing to bear align with patient values.

Personalized, to me, represents a spectrum of definitions to which all are applicable.

Kuntz: Tushar, tell us a little bit about SimBioSys and your approach to personalized medicine.

Tushar Pandey, MBA, CEO: SimBioSys is an early-stage startup out of the Midwest. We’re about 30 people now and take a unique approach toward precision medicine.

Precision medicine is more than molecular diagnostics. Precision medicine is more than, “Based on the tumor, what is the right treatment for that particular patient on that particular day?”

What we’ve developed is a software application called TumorScope that can essentially create a virtual 3D model of a patient’s tumor space from standard-of-care imaging, and then empowers the clinician to be able to test the treatment options that are indicated for that patient, all prior to initiation.

Clinicians can’t take back toxicity. Once the patient has been given a drug, it’s hard to take that away. Getting that right upfront is incredibly important. With the patient at heart, we are serving clinicians who want to assess what the right therapy is for their patient.

We’re also serving the drug development space to bridge the gap between preclinical success and failure in human clinical trials. There is a right drug for patients, whether it passes a clinical trial or not. We are helping pharma companies find that right subpopulation for those patients so that novel therapies are getting to the right people, and faster.

Kuntz: Precision medicine and genomic testing have altered the treatment for cancer over the last several years. What do you see is the role for even more precise, personalized, or even individualized medicine for cancer care? How precise would you want those technologies to be?

Loy: It’s an interesting question because there is a technology looking for clinical utility. I see this as one of many tools to personalize medicine, and to the extent that we can take these types of capabilities that Tushar was talking about and bring them to bear on the experiences and the endpoints that are important to patients.

What does that mean? If I’m living with a cancer diagnosis, and I have a chance of cure, I want what Tushar described. I want minimal toxicity, and I want the information that will give me the assurance that I’m doing everything I can do to be cured and get on with my life. Whereas, if I’m in the metastatic setting or in the incurable setting, I’m looking for the things that are going to give me overall survival or quality of life.

I recognize that we don’t have any perfect tests. At the end of the day, we have an obligation to make sure that the clinicians that are using the tool and the receivers (ie, patients) of those tools understand the limitations and the risks and the benefits, ultimately, before we even go down the road of testing.

There’s a lot here other than looking for an expectation of “Here’s a test result, and that should guide our therapy.” It’s a much more complex conversation, in my view.

Pandey: It’s a tough conversation because the risk-benefit calculus in oncology is so complex. The additional month of therapy could add 2 months of overall survival, but the toxicity during that period is unbearable for some patients.

Reducing 1% risk of a recurrence could give you secondary leukemia or cardiotoxicity for a lifetime. That risk-benefit is incredibly complex. With precision medicine, we really haven’t empowered clinicians to be able to share and collaborate with patients on that risk benefit-calculus in an effective manner.

Loy: Not only is it complex, sometimes it’s unknown. Having tools that help us get to near equivalence or the effectiveness we’re looking for while reducing toxicity, especially early on in life, becomes extremely important.

In our geriatric populations, we’re looking for those indicators that can help folks that may not otherwise have been represented well in clinical trials to at least understand how those drugs are going to perform. There’s a lot of unmet need here that we’re talking about. Bringing these tools to bear will only help us answer these questions more intelligently.

Kuntz: With the advent of personalized medicine, clinical pathways are still the gold standard in cancer treatment selection, certainly for earlier disease stages. They direct as much as 60% to 80% of treatment decisions today. If I understand directly, the goals of SimBioSys and clinical pathways are similar: to help clinicians identify the most appropriate treatment for patients and their disease presentation. How does SimBioSys approach that question differently from existing paradigms, such as pathways?

Pandey: Clinical pathways are trailblazers in this concept of promoting standardization and the use of data and data-driven decision-making. They’ve been incredibly important in this field to help clinicians level the playing field.

Just like any industry, there is a natural evolution that needs to happen. For far too long in oncology, we’ve been treating what’s best for a population. We used to do best for the indication, then we started stratifying on biomarkers of commonly known pathological markers. We’re heading toward the genomic era, where we’re becoming more precise. Pathways bridge some of the gap between indication and biomarker.

At SimBioSys, we rally around the analogy of navigation. For example, using Google Maps, we know exactly where we’re going, how long it’s going to take to get there, better route(s) on that particular day or moment, other roadblocks, etc.

We think of the parallel in pathways as, “Here’s a map of potentially how you get there.” We need to get to the true individualized nature of the patient’s cancer and treatment.

We think of precision medicine very similarly. There are technologies, like genomics, single-cell, or liquid biopsies, and even simpler technologies, like imaging, that are part and parcel. Those needed to be foundationally present and used for us to be able to converge and empower larger group of clinicians over time.

Kuntz: In your experience working with oncologists, what do you see and what do they see as the biggest gaps in treatment planning?

Pandey: Transparency in understanding the “why.” Why would a patient need this therapy vs another? We’re empowering them with data, but that doesn’t answer the question of why, or why a patient will or won’t respond, or why a patient did well to a particular disease. You can’t answer that with just an expression of a gene. You need to answer that with an insight, “Does my patient have a drug delivery issue? Does my patient have a particular receptor that the drug would work better on?”

The reason for it is two-fold. One is to be more confident on decision-making. The other is patients are consumers now, they’re asking questions and want to be part of their care team.

Kuntz: What do you believe are some of the gaps in precision medicine?

Loy: We’ve entered that arena, where folks are asking, “What do the evidentiary requirements need to look like?” We’ve got plenty of examples where we said yes to something and later said, “You know what? It probably did not serve this population as well as or with as much confidence as we thought that it would have.”

Similarly, we’ve experienced the same thing from randomized clinical trials for populations that really aren’t representative of real world. Somewhere in all of this, we’ve got to take an approach to learn our way into and lead a path of no regret to get where we can get comfortable either living with a certain amount of uncertainty or acknowledging that those gaps are the price we’re going to have to pay.

Pandey: Couldn’t agree more. The rate of innovation in this space is so inspiring. There are new things happening every day, but we haven’t been able to measure the impact yet. There is that uncertainty that we live with. Is it good for the patient? Is it good for the physician?

I slightly differ with where the opportunity exists and why precision medicine hasn’t lived up to its promises. The availability and impact have been for very limited populations. If you think about precision medicine today, it has been primarily geared toward advanced stages of the disease with less focus on earlier stages. Any physician or scientist will tell you, if you get things right in the earlier stage, fewer patients will progress to the advanced stage of the disease.

Whether it’s a technical barrier, a financial barrier, or a geographical barrier, precision medicine today is not precision medicine for all. Precision medicine, for it to be impactful, needs to be for all. You need a broader usage of precision medicine to be able to find those cases that are truly benefiting from them.

Precision medicine and individualized medicine need to be broader and understood multidimensionally, just the way the disease is. Precision medicine has been focused primarily on physicians, researchers, and scientists; we’ve missed the orientation toward the patient. There are nuanced ways you do that. How do you make precision medicine understandable to a patient? How do you take that understanding and ultimately lead to a shared decision between the patient and the physician?

Kuntz: Breast cancer has among the highest incidence rates of cancer in the United States. Because of the volume of patients and the rapid advances and broad range of treatment options, do you think breast cancer will remain a major area of focus for the oncology community?

Loy: If I were to anchor any of my thoughts to one concept, it would be overtreatment. As you get into different phenotypic dispersions from the tissue diagnosis and start asking who’s going to benefit from what therapy? What does that sequence need to look like? When can we stop there and let the patient enjoy a drug holiday? I think we’ve got a lifetime of opportunity in front of us just answering some of those questions, not to mention dosing, scheduling, recurrence, etc.

Pandey: The one part I disagree with is the assumption that there’s a strong standard of care in breast cancer. For the same patient, you could have up to 13 regimens that may consist of similar drugs, different schedules, and different doses, all of which may have different responses. Physicians know the standard of care, but physicians also see significant variability or uncertainty in what’s the right decision for a particular patient.

You compound that with the number of drugs that are getting approved in this space, that’s going to completely disrupt—in a really great way—the standard of care for triple-negative breast cancer patients.

There are antibody-drug conjugates like T-DM1 that are showing some amazing efficacy in adjuvant populations. There are drugs like tucatinib that increase the survival in metastatic patients. All of these come with their own risks, alongside the benefit.

Doctors are finding it really difficult to be able to keep up with this evolving standard of care in breast cancer, and it continues to be an area of unmet need, not just from a population perspective, but because of the changing landscape as well.