Penn cancer center looks to expanded gene testing

The University of Pennsylvania's Abramson Cancer Center has raised its bet that the future of cancer treatment lies in our genes.

It is testing the tumors of almost all patients with melanoma and blood, brain, and lung cancers for mutations that could change treatment decisions. The plan is to extend the testing, which looks for 33 to 47 mutations, to all patients within the next year or two.

David B. Roth, who is chairman of the department of pathology at Penn Medicine and a champion of the aggressive approach, said two to three dozen cancer centers in the nation are routinely testing some patient populations for panels of cancer gene mutations. Fox Chase Cancer Center announced in January that it would be offering such testing to patients with advanced cancer who had exhausted standard treatment options. Other area centers are being more cautious.

Penn is doing the testing in both newly diagnosed patients and those with disease that has spread or recurred. It is in discussions with smaller hospitals within its cancer network to perform testing for them at its new Center for Personalized Diagnostics on Market Street near 30th Street Station.

"It's going to be catching fire," Roth said. "In a couple years, I think all academic centers are going to be doing this."

Roth is not alone in thinking that treatments tailored to mutations in a patient's tumor will revolutionize not only care but research. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society, is concerned about fueling "hope and hype," but sees genetics as a "game changer" in cancer. "This is gee-whiz science that I think is actually going to make a difference," he said.

It is already standard practice in some cancers to test for individual mutations known to affect prognosis or response to drugs. Doctors anywhere can order genomic tests from private companies like Foundation Medicine. Now in a quiet period as it prepares to sell stock, Foundation Medicine estimates the market for comprehensive molecular cancer tests at $4 billion now and $7.5 billion in the next "several" years.

The spike in interest in tumor testing coincides with the growth of targeted therapies that home in on genetic differences that help cancer cells proliferate wildly. Hundreds of targeted drugs are in the testing pipeline.

"In the last three years, the field has been transformed by discoveries of new mutations and new therapies," said Lynn Schuchter, Penn's chief of medical oncology, who specializes in melanoma. In May, for example, the FDA approved Dabrafenib and Trametinib, drugs that target BRAF and MEK mutations.

"This is not a cure," Schuchter said, adding that new immune therapies are also getting good results. "It's a huge leap forward, but it's not the final answer, and we still have more work to do."

In contrast, chemotherapies kill all cells that grow rapidly - not just cancer cells. That is one reason their side effects can be so debilitating.

The eye-glazing lists of mutations the tests reveal may revolutionize the way we think about cancer. Instead of considering cancer in each organ separately, scientists already are grouping cancers with the same mutations in different organs in "basket" or "bucket" clinical trials.

For now, the ability to identify differences in tumor cells far outstrips the ability to do anything about them. Patients could learn they have mutations for which there are no approved treatments. This may help them pick a clinical trial, but it might also make them want to try a drug that their insurer won't pay for.

"That will lead to enormous anxieties for many people," said Arthur Caplan, a bioethicist at New York University. He sees the tests as promising "if for no other reason than to avoid exposing people to noxious agents that won't benefit them."

Penn said insurance generally covers the $2,000 to $2,500 cost for its genetic panel. Foundation Medicine, whose test looks at 236 genes, charges $5,800 and says coverage varies.

Researchers are learning that the more they find out about cancer genes, the more they need to know. Drugs don't necessarily work the same way on the same mutation in different organs. Cancer cells still learn how to evade the targeted therapies, so the trick may be to craft cocktails that attack multiple weak points.

"The danger is the overpromise, the perception that the public may think we've got it all figured out," said Carlos Arteaga, the American Association for Cancer Research's president-elect. He wondered whether tests make sense for all cancer patients, given that some can already be treated successfully.

At Penn, where 375 people have gotten the tests since February, Roth is focusing on clinically "actionable" results. That means results that help doctors choose a treatment or trial or rule out a treatment, such as a bone marrow transplant, that is unlikely to help.

"We are practical people," Roth said. "This is not meant to be primarily a research enterprise."

Meanwhile, Jeff Boyd, executive director of the Cancer Genome Institute at Fox Chase, says only 20 to 40 patients there have had the genetic panel done. He's most interested in using the tests to bolster research. "We're really ramping up genomically informed clinical trials," he said.

Stephen Peiper, chairman of the department of pathology, anatomy, and cell biology at Thomas Jefferson University, said Jefferson is using the tests, but cautiously. "This is a very powerful technology," he said, "and I think we're in the process of learning how to use it."

Maurie Markman, national director of medical oncology at Cancer Treatment Centers of America's Eastern Regional Medical Center in Philadelphia, said he is most likely to use the tests to find potential, and experimental, treatments for patients who have exhausted standard options. Then, he advocates talking to insurance and drug companies about helping to defray costs while doctors track results in a public registry. That will help everyone learn more quickly whether the drug that helps a mutation in, say, breast cancer also works in lung cancer.

"We now have information that is so powerful that we have to start using it, even if we don't know how yet," he said.

Boyd said Fox Chase has started its own registry. There is talk of sharing data nationally. Arteaga favors the idea, too, but says empowering every physician to be an investigator will bring its own challenges. "What do you call a response when you have a million scorers with different levels of training?" he asked. "It gets to be pretty emotional, frankly."

Nicholas Petrelli, medical director of Christiana Care Health System's Helen F. Graham Cancer Center, said that Christiana has started using genetic panels very slowly, but he said that the nation's resources could be better spent elsewhere. Using the tests to identify targeted treatments may only extend life a little. The real return is in preventing cancer by getting people to stop smoking, maintain a healthy weight, use sunscreen, and get colon cancer screening.

But Schuchter said patients want to know about new therapies and clinical trials. "Patients are hungry for this," she said. "They are asking to know more about their tumor."