From research lab to exam room: Bringing precision medicine into focus


Will Seaton

Essential Insights contributor, healthcare writer

According to the National Institutes of Health, precision medicine is "an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person."

The term became a healthcare buzzword after President Obama used it in his 2015 State of the Union address, announcing the launch of the Precision Medicine Initiative ( PMI ). And with the recent $1.5 billion federal funding injection into the PMI and its one million volunteer cohort research program All of Us —via the 21st Century Cures Act —the idea has been thrust further into the national spotlight.

While the concept of tailoring treatments to an individual patient’s needs is nothing new in medicine, advances in science and technology, including the decreasing costs of genomic sequencing and the accessibility of big data, have fueled more efforts around precision medicine. Today, much of the discussion around precision medicine revolves around cancer genomics — understanding the genetic profile of each patient’s cancer and what treatment strategies may work best.

Precision medicine’s impact on cancer

“We have evolved our understanding of cancer from that of a diseased organ, which must be removed to be cured, to a cellular disease that spreads through the lymphatic and blood systems, and now to a genomic disease, where mutated genes governing particular molecular pathways lead to developing cancer.” said Dr. Bruce Feinberg, vice president and chief medical officer for Cardinal Health Specialty Solutions.

Feinberg added that this evolution in understanding has transformed cancer care, as breast cancer treatment illustrates. He explained that when cancer was believed to be the result of a diseased organ, the treatment for breast cancer was radical mastectomy. When cancer was understood to be a cellular disease, treatment for breast cancer shifted to the lumpectomy, with or without chemo-hormonal therapy to kill the microscopic cells circulating outside the breast. As we gain further understanding of cancer’s genomic basis, treatment standards are likely to change again.

The critical insight of precision medicine is that mutations within the cancer genome result in altered protein expression that can give rise to unique, readily identifiable molecular targets within, or on the surface of, cancer cells. These specific targetable proteins may not be limited to one type of cancer. "Some mutations are commonly found in a variety of cancers, can be present in both genders, in different histologies, and so forth," explained Dr. Chadi Nabhan, vice president and chief medical officer for Cardinal Health Specialty Solutions. "For example, one target, one mutated gene called Her2 is found in both some breast cancer and some stomach cancer patients, and these patients are being treated with the same drug. Twenty years ago, that was unthinkable."

So far, multiple targeted therapies have been approved by the Food & Drug Administration to treat a variety of cancers. Many more currently exist in late-phase clinical trials. Precision medicine has shown success in the treatment of small diseases subsets. For example, the drug Gleevec (generic name Imatinib) approved in 2002 to treat chronic myeloid leukemia appears to cure or control disease in the majority of patients who otherwise would have had a limited life expectancy of less than five years unless transplanted successfully. This so-called “medical miracle” created unbridled optimism for the precision medicine approach, which over the past two decades has seen other successes, but not on the Gleevec scale.

So now the question is: Will targeted therapy of cancer be the revolution it was once believed to be, or will it be eclipsed by the emerging field of Immuno-oncology? And more importantly, will these therapies be safer and more effective treatments than chemotherapy in the broader cancer patient population? Precision medicine argues that treating the “target” is a better, safer, and potentially more cost-effective strategy. Data to support this hypothesis remain sparse and studies are ongoing.

Barriers to precision medicine

"We have to acknowledge that for the majority of precision therapeutics, we don't yet know whether this is truly leading to better patient outcomes," noted Dr. Nabhan. "This is especially critical in a value-based care environment, where we have to clearly demonstrate the clinical value of given therapies, in terms of outcomes versus cost. We recognize that today in many cases, it’s a more expensive, but not necessarily better, way to treat cancer."

To help doctors and patients assess the relative value of cancer treatments, the American Society of Clinical Oncology released a value framework that looks at new cancer therapies based on clinical benefit, side effects, and improvements in patient symptoms or quality of life in the context of cost. The National Comprehensive Cancer Network proposed utilizing "Evidence Blocks”TM as a method for providers and patients to engage in a shared-decision making dialogue, so that the most appropriate therapy for a given patient is dispensed. How such value tools will impact stakeholder decision making remains to be seen, but they introduce a change in how treatment pathways and standards of care will likely be considered in the future.

Moreover, targeted therapies, while effective in some cancers, still lack efficacy in others — due in large part, perhaps, to the sheer intricacy of the disease environment. "We almost have to think about each cancer as unique unto itself, and, unfortunately, we don't always have a strong basis for intervention through a targeted therapy," explained Dr. Feinberg.

For TJ Bowen, a cancer geneticist and director of innovation solutions at Fuse by Cardinal Health this is the, "billion dollar question." He said that, "Each person is unique. Every time we think we've thought of the most elegant solution, the human body proves that no single approach will work." Still, he believes that there are plenty of reasons to remain optimistic.


Precision medicine in practice

One promising research area has been in the use of data analytics. At Fuse, Bowen is working to develop technology that can leverage data insights gleaned from broad medical ecosystems including clinician networks, large cancer centers, and group purchasing organizations. This data can help physicians pinpoint the specific, evidence-based therapies most beneficial to their patients.

"If a specific patient looks similar, in profile, to patients beyond an oncologist’s clinic, the data may show that patient will respond best to a very specific therapy," Bowen said. "This allows physicians to apply evidence beyond their own empirical experience in support of clinical decisions." Such technologies could play a large role in demonstrating the applicability of precision medicine treatments to the physician community.

For example, the largest clinical study of pediatric brain tumors recently found that a majority could possibly be treated with targeted therapies.

Next steps for precision medicine

Precision medicine has become part of treatment discussions. "The conversations that oncologists had with patients 30 or 40 years ago are very different than the conversations that oncologists are having now,” Dr. Nabhan observed. "Just six years ago, we didn't have the technology, the knowledge, or the science for precision medicine." Yet more work needs to be done to see if targeted therapies can provide safer and more effective treatments than the predominant options.

While the promise of precision medicine is not yet fulfilled, patients and providers will all be watching to see what advancements may come next.

Spotlight on value calculators for specialty drugs

A look at “value calculator” methodologies to measure and compare the overall value of cancer therapies.