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Indi Publishes Second Clinical Validation of Xpresys Lung, Turns Focus to Proving Clinical Utility


NEW YORK(GenomeWeb) – Integrated Diagnostics this week presented results from a second clinical validation study of its Xpresys Lung cancer test.

Published this month in the Journal of Thoracic Oncology, the study, which looked at 141 blood samples from patients 40 years or older with lung nodules ranging between eight and 30 mm in diameter, found that the test could identify benign lesions in lung cancer patients with a negative predictive value of between 84 percent and 98 percent.

Additionally, the study confirmed previous findings that the test classifier worked independent of patient age, smoking history, nodule size, or chronic obstructive pulmonary disease diagnosis, making it an independent complement to these traditional risk factors assessments. 

The study follows an initial validation study the company published in Science Translational Medicine in 2013, weeks before commercial launch of the test. That study looked at 104 samples from four sites, finding that the test could identify benign lesions with NPV of 90 percent.

Xpresys is intended to aid doctors in identifying lung nodules detected via CT scans as likely benign. The test uses multiple-reaction monitoring mass spec to quantify the levels of 11 proteins in patient blood samples.

In addition to the two validation studies, Indi is currently undertaking two prospective clinical studies that are aimed at further characterizing the test as well as establishing clinical utility, CEO Al Luderer told GenomeWeb.

The first of these two trials has been completed and is being used as the basis of the company's application to the Centers for Medicare & Medicaid Services for coverage of the test, Luderer said.

That trial looked at more than 400 patients with suspicious nodules who physicians advanced to surgery.

The second trial is looking at roughly 700 patients, and, Luderer said, "will likely become an important reference for what actually happens with management of these nodules and how our technology will help manage a better outcome."

The rationale for Xpresys is that, by identifying nodules that are likely benign, physicians can more comfortably put patients on a regimen of watchful waiting. A non-invasive test like Xpresys is desirable due to the expense and significant risks of the invasive procedures currently used for determining lung cancer status, like fine needle aspiration and thoracotomies.

Indi has hit significant milestones since launching Xpresys in 2013, particular on the reimbursement side of things, where the company this fall announced it had secured more than 200 million covered lives for the test.

However, Luderer said this week that the company faced a challenge in getting physicians comfortable with the probabilistic nature of the test.

"I have to admit that providing a test that gives a probabilistic value is still kind of a new thing for docs," he said. "It has been interesting to give them a mathematical number that says, 'you're most likely benign.'"

This reflects comments made at the time of the test's launch by some physicians who indicated that doctors might be uncomfortable relying on a test that left even a small amount of doubt as to whether a lesion was benign. 

For instance, Howard West, a thoracic oncologist atSeattle's Swedish Cancer Institute, suggested that the test's low positive predictive value could, in fact, lead to higher numbers of follow-up scans and invasive procedures, rather than fewer.

Indi has been quite clear that the Xpresys test is intended only to rule out the possibility of cancer, with indeterminate or positive results not to be taken as indicating that a nodule is cancerous. "The problem is," West said, "that's not the way the world works."

"If you have somebody who has a nodule and the test comes back as anything other than negative, I think it is going to be human nature that the patient or doctors are going to potentially be far more likely to escalate the work-up and now do biopsies when they otherwise wouldn't have, or do scans more frequently than they would have," he said.

Comments from Peter Mazzone, a pulmonologist at Cleveland Clinic who was involved in collecting samples for one of Indi's clinical trials, noted as well that the test might realistically be applied only to a small proportion of the patients that technically fit within its use guidelines.

For instance, he said, he would consider ordering the test in the case of "a patient who is otherwise somewhat ill and may not do well with a biopsy."

On the other hand, "if it's a very healthy person [in] whom I don't want to miss a cancer regardless of what the blood test tells me, then I probably wouldn't order it," he said.

In total, Mazzone estimated, less than 10 percent of his patients fit the criteria under which he would consider ordering the Xpresys test.

Luderer noted this week that these were "not unusual" physician comments regarding the test. He said that he expected the two prospective trials underway would help ease such concerns.

The comments "reflect the underlying fear that there is a cancer," he said. "But for patients in this range, only one out of five have a cancer, and this group of patients get enormously overworked, and there is a lot of morbidity and mortality associated with the [conventional] decision process."

Luderer said Indi has submitted a paper to the Annals of Internal Medicine that aims to show why a test like Xpresys is needed. Still awaiting review, the paper finds that in community-based practices 35 to 50 percent of Xpresys' intended patient population who go on to surgery have a benign lesion, he said, adding that "when you go in for surgery of this type there is a mortality rate of up to 3 percent."

"So it's a matter of getting physicians comfortable with this [test], helping them understand where it is best deployed and in [which] patients," Luderer said.