Precision Medicine Is More Than Genomic Sequencing

Robert H. Carlson, MBA


October 24, 2016

SHIVA Calls Molecular Profiling Into Question

A controversial clinical trial published in 2015 questioned the value of molecular profiling in precision medicine.[1]

Researchers in the phase 2 SHIVA study assessed the efficacy of several targeted agents marketed in France, chosen on the basis of tumor molecular profiling but used outside their indications, in heavily pretreated patients with cancer.

The authors concluded that the use of molecularly targeted agents outside their indications did not improve progression-free survival compared with treatment of physician's choice, and recommended that off-label use of molecularly targeted agents should be discouraged.

A US oncologist disagreed strongly with that assessment.

"Some say the SHIVA trial shows that precision medicine doesn't work—that's just ludicrous," said Maurie Markman, MD, president of Medicine and Science at Cancer Treatment Centers of America in Philadelphia, in an interview. "Anyone who criticizes the concept of precision medicine simply does not understand it."

Markman said that unfortunately, precision medicine is seen by some as being an event: "In other words, at some point in time, one would declare that we have shown that precision medicine works. That is not what it is about; it is a process, and we are increasingly learning about the relevant targets in individual tumors and tumor types."

"That's going to be the future of the cancer care continuum, there is no question about it," he said. "We may not understand the targets—and even if we do understand the targets, we may not have the right drugs—but this is a process, and we will continually move forward. The point of precision medicine is that we are looking at the tumors themselves to try to understand them, and it may be a long time before we have an impact."

Massimo Cristofanilli, MD, an associate director for Precision Medicine and Translational Research at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, said that some people might believe that precision medicine cannot be a solution for a complex disease such as cancer, but he said precision medicine cannot be oversimplified.

"The more we get into the details of understanding the biology of the disease with the various molecular tests, it is clear that it is much more difficult to apply this information to change patient outcome than we believed it was going to be," Dr Cristofanilli said.

"We need to rethink how to design trials to look at the efficacy of these interventions," he said. He pointed to the NCI-MATCH (Molecular Analysis for Therapy Choice) phase 2 precision medicine trial as a good start. NCI-MATCH seeks to determine whether matching certain drugs or drug combinations in patients whose tumors have specific gene abnormalities will effectively treat their cancer, regardless of their cancer type.

Dr Cristofanilli said this is in contrast to some commercially available genomic assays that have been oversold.

"According to the first page of the [commercial assay] report, the test will be 'a solution with one easy approach to precision medicine,' but in fact it is a much more complex situation," he said. "A better approach will be academic institutions with molecular tumor boards with a multidisciplinary approach, and even better will be multiple institutions working together."

"Molecular tests, yes, but in the context of the disease and the therapy for that particular disease," Dr Cristofanilli said.


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