A number of pharmaceutical companies are using the test in clinical trials of new drugs. For example, if a study of a specific new drug failed to show a benefit in the patient population overall but did appear to work in a subset of patients, researchers can use Foundation Medicine’s test to determine if there is a particular genetic alteration that predicts who is most likely to respond.
Companies are also using the technology to direct patients into specific studies of drugs designed to target different mutations; it can often be difficult to enroll enough patients in such studies. Furthermore, if researchers collect multiple tumor samples from the same patient over time, they can use the test to understand how the tumor evolves and try to predict why one person’s tumor might recur more quickly than another’s.
Pellini says at least two pharmaceutical companies are considering using the technology in all cancer clinical trials going forward. “Pharma’s willingness to accept this type of molecular approach has been my single greatest surprise since joining Foundation Medicine,” he says. Historically, the pharmaceutical industry has been reluctant to test drugs in only a subset of patients, because this limits the number of people who might buy the drug.
“There has been a transformation among many pharmaceutical companies to where they understand that targeted therapeutics is the new paradigm,” says Pellini. Targeting clinical trials to only the patients who are most likely to respond to a drug makes it faster and cheaper to show that a drug works. “As everyone works to turn cancer into a chronic disease, as an industry, we will have the ability to treat patients for years rather than months—pharma has caught on to those concepts,” he says.
Because Foundation Medicine’s test is based on sequencing genes, rather than detecting known mutations, it can also find novel genetic changes. “As a by-product, a lot of novel discovery is coming out of these efforts,” says Pellini. “We are identifying novel gene fusions, translocations, and mutations, many of which have clinical significance.”
For example, researchers at Foundation Medicine identified a genetic translocation—where a segment of DNA is flipped around—in cancer tissue from a patient with non-small-cell lung cancer. Subsequent studies found that this mutation, which lies in a part of the genome that is being targeted by pharmaceutical companies, is present in about 5 percent of small-cell lung cancers. Pellini says the company is still working on how to deal with such new discoveries. “We are not a therapeutic company, and our primary interest tends to be on the diagnostic side,” he says. “But we recognize that some findings may have strong therapeutic implications.”