Guest Blog
by Jennifer Levin Carter, M.D., M.P.H.

Jennifer Levin Carter, M.D., M.P.H.

The introduction of next-generation sequencing (NGS) into the clinic is transforming cancer care. The deeper understanding of the drivers of disease facilitated by these tests enables greater precision in determining the therapeutic strategy for each patient.

Growing access to molecular testing has also created a new challenge for the physician. Each NGS test, whether examining 10, 50, 100 or 1000 genes, produces an overwhelming amount of molecular data. In addition, other molecular test results, such as those evaluating copy number alterations or protein expression, also need be integrated. New research on molecular targets in oncology and new targeted therapies are published every day. The available data continues to grow exponentially in both volume and complexity.

The key challenge for clinicians is how to efficiently harness all of the molecular data produced by the NGS and other tests, even for small panels of 10 or 15 genes, in order to gain the most insight and value relevant to selecting a therapeutic strategy for each patient. For example, a melanoma patient with a BRAF V600E mutation could benefit from the FDA-approved drug vemurafenib, but clinical trials have demonstrated that a colorectal cancer patient with the same mutation is not likely to benefit from this drug as a single agent. A patient with an activating ERBB2 mutation in non-small cell lung cancer may benefit from trastuzumab, a drug that was approved for breast cancer patients with ERBB2 amplifications but not ERBB2 mutations. This challenge is compounded by the rapid growth in the number of therapies available on the market and in the number of clinical trials available.

Patient-specific clinical interpretation addresses these challenges by providing the physician with the clinical and scientific evidence that is the critical link between the molecular data generated by the NGS and appropriate therapeutic options. Clinical interpretation uses the molecular test data generated from each patient’s tumor profile after having been filtered by the bioinformatics pipeline, and assesses the molecular effect of each individual’s clinically relevant alterations as well as the combination of alterations in the context of each patient’s cancer subtype to determine the link to possible relevant therapeutic strategies. Treatment strategies can include FDA-approved on-label therapies, off-label therapies, and therapies in clinical trials.

The clinical interpretation of a patient’s molecular data often uncovers evidence that suggests that the most relevant therapy for a patient is only available in a clinical trial. As the complexity of the molecular data continues to grow and our understanding of the data evolves, so too does the complexity of clinical trial design. Thus, physicians lack the time required to research and identify trials suitable for each patient. Online and public resources do not provide the detailed analysis needed to help physicians and patients identify the relevant targeted therapy trials for which they would be “molecularly eligible^TM”.

To find relevant trials for a cancer patient:

• Gene, variant and disease-specific analysis is critical for making the right trial match.
• Multi-variant analysis is required to understand drug resistance, drug sensitivity and the potential for combination therapies.
• Trials need to be chosen based on the molecular features of the drug and each arm of the trial.
• Patients must also be matched based on their location—they prefer generally to enroll in trials at the institutions where they are being treated. Otherwise, at a hospital that is close to home.
• The physician needs easy access to the clinical and scientific evidence supporting the particular trials to enable efficient discussion with the patient about relevant trials.
• Additional services may be required to close the loop for the patient and physician on connecting with the trial site.

Thus, expert clinical interpretation decreases the barriers to clinical trial enrollment by rapidly delivering the analysis of each patient’s molecular data and the relevant list of appropriate clinical trials directly to the point of care.

Intermountain Healthcare has conducted two studies that demonstrate that providing physicians with N-of-One’s patient-specific clinical interpretation enables a physician to utilize the molecular data to make additional treatment decisions. ^1,2 In these initial studies, armed with the necessary information, treatment management changed in more than 70% of cases where molecular testing and N-of-One clinical interpretation were available. ^1,2

In the coming months and years, molecular testing will play an increasingly valuable role in the treatment of cancer. However, the complexity of using molecular testing will continue to grow exponentially with new tests, new drugs and thus new knowledge continually emerging. Physicians need ready access to “physician-ready” knowledge to efficiently utilize the molecular data to make precision medicine a reality for their patients.

1 Nadauld et al., J. Clin. Oncol. 33, 2015 (ASCO Abstract e17647)

2 Nadauld et al., J. Clin. Oncol. 33, 2015 (ASCO Abstract e17641)

—
Jennifer Levin Carter, M.D., M.P.H.
Founder, Chief Medical Officer
N-of-One

The PMC/BIO Solutions Summit took place at the Renaissance Hotel in Washington, D.C.

Personalized medicine can provide safer, more effective treatment options for patients and potentially reduce health care costs, but the best practices for integrating personalized medicine into an existing health care system are not yet clear. The Personalized Medicine Coalition (PMC) and Biotechnology Industry Organization (BIO) Solutions Summit: Integrating Personalized Medicine into Health Care helped to fill this knowledge gap, revealing a range of solutions to challenges facing the field. They encourage a fundamental change in the way medicine is practiced, from population-based, trial-and-error methods to a more personalized approach based on the use of an individual patient’s molecular information.

Five Solutions to Help Integrate Personalized Medicine into Health Care

1. Provide scientific and value-based evidence that is customized for each audience (payers, providers, patients).

Personalized medicine is scientifically complicated, and industry-generated evidence that demonstrates clinical and economic value is sometimes hard to understand or impractical to use. Product developers should generate and customize evidence reports for each audience (i.e. payers, providers, patients) that highlight easily understood scientific information and demonstrate improved outcomes.

2. Educate broadly.

Both the health care workforce and patients need a better understanding of personalized medicine. Freely accessible online materials can help build a stronger knowledge base. Patient support groups can help patients understand molecular mechanisms of disease and the benefits of personalized medicine technologies. Physician and community leaders can be identified and provided with the resources they need to raise awareness and advocate for change.

3. Develop proactive policies that incentivize a learning health system and the adoption of personalized medicine products based on their value.

The current policy environment often incentivizes health care practice based on volume rather than value. Outcomes data must be systematically collected and shared to help expand the understanding of high-value technologies, and policies need to be developed and implemented that reward health care providers for optimizing treatments based on individual patient characteristics.

4. Provide information about clinically actionable variants that accompanies individual medical data, and link it directly to electronic medical records.

Turning the large amounts of data associated with personalized care into comprehensive, useful and user-friendly information is challenging. Information on clinically actionable data points should accompany medical data in electronic health records so that providers can separate signals from noise. Clinical support information must be presented in a way that saves time for physicians, and must allow for expansion that can keep pace with the rate of scientific advancement.

5. Ensure that policies and practices that address ethical, legal and societal issues are acceptable to patients.

Personalized medicine raises a new set of ethical, legal and societal issues regarding the use of individual molecular information. Policies and practices related to the use of individual molecular information must be developed with patient input, and before issues arise.

PMC has convened a group of expert leaders to articulate these challenges and solutions. The group plans to publish a best practices guide that can help speed the integration of personalized medicine into health care systems.

Guided by these strategies, it is our hope that many providers see the future within reach.

—
Daryl Pritchard, Ph.D.
Vice President, Science Policy
Personalized Medicine Coalition