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Blood Simple? Grail’s Cancer Screening Quest Faces Tough Questions

Xconomy National — 

[Corrected, 2/4/16, 2:05pm. See below.] Three weeks ago the world’s biggest genomic sequencing company, Illumina (NASDAQ: ILMN), unveiled a spinout called Grail to make blood tests that could spot all kinds of cancer in seemingly healthy people, perhaps as soon as 2019.

If you know anything about the history of screening healthy people for cancer, you’re right to be skeptical.

The people behind Grail can sympathize. “I was the in-house skeptic,” says Rick Klausner, Illumina’s chief medical officer since 2013. “I told Illumina, ‘Don’t go near it.'”

Klausner, who has also run the National Institutes of Health’s National Cancer Institute and was the top global health official at the Bill and Melinda Gates Foundation, has changed his tune.

But from conversations with Klausner and many others in the field of cancer research, treatment, and prevention, it’s clear that the scope and audacity of Grail’s plans will require measurements and analysis that stretch the understanding of biology, as well as strategies that run counter to much of the current thinking in public health.

“In the past we’ve made promises to the public that didn’t go well,” says Scott Lippman, director of the University of California San Diego’s Moores Cancer Center, speaking about the cancer medical field. (He is not affiliated with Grail.) “Given the molecular complexity of cancer and its premalignant origins, this is a big promise to say we’ll take a drop of blood, tell you if you have cancer, where it is, and how we might cure it.”

Grail launched last month with more than $100 million committed from Illumina, which is majority owner, Arch Venture Partners, Sutter Hill Ventures, Bill Gates, and Bezos Expeditions, the umbrella organization for Amazon.com founder Jeff Bezos’s extracurricular interests and investments.

Illumina warned investors its earnings per share would dip by 15 cents this year because of its Grail investment. It’s only a 3 or 4 percent drop, based on Illumina’s own estimates, but it’s tangible.

Grail has yet to name a CEO. An announcement could come soon. So it was Klausner, a Grail board member, who spent time on the phone with me last week to explain how Grail intends to develop a blood test that combs through the entire genomes of healthy people for the faintest traces of cancer—even tumors that are too small to cause symptoms or be detected in other ways.

Grail must also prove to doctors, patients, health regulators and insurers that its high-tech detective work actually results in better outcomes for patients. The need to make people’s lives better cannot be overstated. “The major challenge in early cancer detection is that there is always harm to some degree, no matter what the screening test,” says Lippman. “So the amount of benefit you have to show must be even higher.”

For decades, many clinicians, medical societies, and advocacy groups like Susan G. Komen have urged healthy people to undergo regular testing for various cancers. Screening saves lives, goes the mantra. Problem is, most tests have made it into wide use without first undergoing the long-term, randomized trials that many researchers believe are the definitive way to show that a test actually saves lives rather than, for example, uncovering tumors that were never destined to spread or otherwise harm the patient.

What’s more, screening can hasten death or injury through unnecessary biopsies, surgeries, and drug regimens for people wrongly diagnosed or whose cancer might never have progressed.

Take, for example, the prostate-specific antigen, or PSA, screen that was once a staple of men’s annual checkups. At best, one in 1,000 men avoids death from prostate cancer after taking the test, according to U.S. Preventive Services Task Force, a volunteer group of medical evidence and prevention experts overseen by the U.S. Agency for Healthcare Research and Quality (AHRQ).

But of those 1,000 men, 30 to 40 will develop erectile dysfunction or incontinence, two will have a heart attack or other serious cardiovascular event, and one will develop a serious blood clot—all from the cancer treatment. These numbers don’t even count complications from invasive biopsy. Given this unfavorable balance of benefits and harms, the Task Force now recommends against routine use of the test.

“The point of screening is to reduce suffering and death, not just to find more stuff,” says Jennifer Croswell, medical officer at the AHRQ.

So here comes the liquid biopsy: a run-of-the-mill blood draw to catch rare bits of DNA and similar molecules shed by a patient’s cancer cells and analyze the mutations in them. Liquid biopsies are starting to gain acceptance as a way to help doctors care for patients already diagnosed with cancer—to help guide treatment based on the tumor’s genetic profile, for example, or to monitor a patient’s response to a drug regimen or surgery.

But is there enough cancer DNA floating around in the blood to red-flag microscopic tumors in otherwise healthy people? Even if Grail—or its competitors in the cancer screening race—could produce a test that was 100 percent reliable at detecting cancer (a statistical impossibility, but let’s just say), could it distinguish between a slow-growing, non-threatening tumor—a turtle, as Croswell puts it—from a fast-growing, dangerous cancer—a rabbit? And could the test makers eventually prove their tests are reducing suffering and death, not just finding more “stuff”?

Grail says yes to all of the above, and company officials say the first … Next Page »

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