Sorting Through a Complicated Precision Medicine Landscape

Sorting Through a Complicated Precision Medicine Landscape

The explosion of precision medicine and genomics research over the last decade or more has revolutionized the field of oncology. Genetic tests ranging from small mutational assays to next-generation whole-exome sequencing are now readily available to clinicians, introducing a new set of complex decisions to oncology clinics.

Two Education Sessions will offer updates on genomics research along with practical advice about how to incorporate precision medicine techniques into practice.

Dr. Lee S. Schwartzberg
“There has been a proliferation of different tests, and there have been lots of claims made about how to use the results of those tests,” Lee S. Schwartzberg, MD, FACP, said. Dr. Schwartzberg will chair the Education Session “Incorporating Precision Medicine Into Your Practice: How, Why, and When?” to be held on June 4.

“The goal is to address, in particular, the community oncologist who may not have been involved in many of the trials or development of this technology and to try to give some clarity from a practical perspective on how to use precision oncology in their practice today,” Dr. Schwartzberg said.

Who, When, and Which Test?

Dr. Schwartzberg will deliver the first talk of the session. He will discuss some of the recent history of precision medicine research and development, the technical aspects involved with molecular profiling, and what to expect from next-generation sequencing tests, among others.

Dr. Schwartzberg will also address a number of questions that arise in everyday practice, including who should be tested, when they should be tested, how oncologists can incorporate a molecular tumor board, and how data from molecular testing integrates with electronic health records.

He noted there are now a number of resources to help oncologists learn how to interpret molecular testing, including the monthly Molecular Oncology Tumor Boards from ASCO University.

Edward S. Kim, MD, of the Levine Cancer Institute, will also speak during the Education Session, drilling down into one specific area where precision medicine has become crucially important: non–small cell lung cancer (NSCLC).

Dr. Kim’s talk “will be a practical case example of how you would use precision oncology in the clinic today,” Dr. Schwartzberg said.

Patients who present with metastatic NSCLC that harbors an EGFR mutation are now treated with EGFR inhibitors, such as erlotinib. However, Dr. Schwartzberg noted that even in that setting, there are practical considerations to molecular profiling—because it can be important to start therapy quickly, understanding which tests to use and when to schedule them can be an important piece of treatment.

In many other malignancies, although there are available tests looking for a variety of mutations and molecular signatures, the tests are not necessarily useful in practice. Dr. Schwartzberg noted that in early-stage cancer, molecular testing is often not predictive of responses to therapy, based on existing evidence. Testing at the first diagnosis of metastatic disease, however, can help clinicians not only choose a primary therapy but also help them plan multiple lines of therapy ahead.

“As we move into this chronic-disease paradigm, trying to think multiple lines of therapy ahead and having the molecular information at hand is important,” Dr. Schwartzberg said.

During the session, Deborah Schrag, MD, MPH, of the Dana-Farber Cancer Institute, will give a discussion of precision oncology in the era of value-based medicine approaches. She will discuss the evidence regarding costs and benefits of some of the available tests, as well as ongoing clinical trials in the field, such as NCI-MATCH, TAPUR, and Lung-MAP.

The session will end with a panel discussion. In general, Dr. Schwartzberg said, the panel will try to offer some guidance into a tangled field.

“Do you want a single-mutation test, or do you want a next-generation multiplex sequencing test? Do you want to do a 35-gene hotspot assay, or do you want to do a test that looks essentially at whole exomes? How do you integrate mRNA or transcriptome testing in there, and what are its advantages?” Dr. Schwartzberg said. “It’s a complicated and rapidly developing field.”

Germline Mutations and Novel Trial Approaches

Another Education Session will look specifically at certain types of mutations and what clinical trials are teaching us about how to approach those mutations in terms of further research and in the clinic today.

Dr. Jorge S. Reis-Filho
The session, “Cascade Testing: What to Do When Ascertaining Germline Mutations From Tumor and Other Genomic Testing,” will be chaired by Jeff Boyd, PhD, of Florida International University, and will take place on June 6.

Neal Ian Lindeman, MD, of Brigham and Women’s Hospital, will speak on tumor genomics in research and clinical practice, and Jorge S. Reis-Filho, MD, PhD, of Memorial Sloan Kettering Cancer Center, will discuss the relationship between tumor subtypes, organ of origin, and driver genes.

“One of our major tasks is to educate the users of the genomic information so that informed decisions can be made in an appropriate manner,” Dr. Reis-Filho said. “At the moment, there is so much uncertainty, and some users don’t have the required knowledge to make the most out of it, so education is absolutely critical.”

Dr. Reis-Filho will provide an overview of large-scale consortium trials that continue to shed light on important questions in precision oncology. These include the SAFIR trials and the MOSCATO 01 trial; the latter showed last year that approximately one-third of patients with advanced or metastatic disease of a variety of primary tumor types have improved survival when high-throughput sequencing is used to guide clinical decisions.

Dr. Reis-Filho pointed out that despite that sort of success, according to available data, there are still a substantial number of patients who may not benefit from precision approaches.

“We had a lot of hope, but, unfortunately, a lot of hype, in precision oncology,” he said. “I am afraid that it may not be the panacea that some people were expecting.”

Although it has dramatically altered therapy in certain malignancies—NSCLC, melanoma, and some hematologic malignancies and rare cancer types, to name a few—the use of genomic testing still has not yielded major changes in others.

“At the moment, we are still writing the book as we go along,” Dr. Reis-Filho said.

He noted that more effort should go into concepts such as basket trials, where patients sharing a specific set of genomic alterations are treated based on that profile rather than the site of disease origin. Dr. Reis-Filho will also discuss some of these approaches during the session.

“There are many opportunities going forward, but we ought to learn the lessons of the first phase of our initial attempts to deliver on the promises of precision medicine,” Dr. Reis-Filho said. “But I am incredibly hopeful.”  

–David Levitan

*Program information updated as of March 15. For session time and location information, please refer to the ASCO iPlanner on the Attendee Resource Center.