Cancer Hospitals Make Gene Tests a New Standard for Care

[CindyA]

“In some cases the disease is very, very aggressive and you don’t have the time to do trial and error, because the patient will progress rapidly,” said Jose Baselga, physician-in-chief at Memorial Sloan Kettering. Source: Memorial Sloan Kettering Cancer Center via Bloomberg

Pinpointing the genetic changes that cause cancer has been a focus of researchers for more than a decade. Now, top cancer hospitals are making genetic testing a new standard of care in the field.

When patients leave Memorial Sloan Kettering Cancer Center in New York after a biopsy, a sample of their tumor takes a different path. It travels across the street to a new laboratory, opened last month, where it will be tested for 341 genetic mutations, so-called biomarkers that will help doctors determine which drug may best help each patient, based more on their genetic profile than where the tumor appears.

As researchers meeting at the American Society of Clinical Oncology in Chicago offer new data from dozens of studies on cancer genetics, clinicians in hospitals including Sloan Kettering, the Dana-Farber Cancer Institute in Boston and others are moving quickly to translate study findings into everyday care based on the biomarkers.

“It’s going to fast-forward progress,” said Kenneth Anderson, director of the Jerome Lipper Multiple Myeloma Center at Dana-Farber, in a telephone interview. “We can select patient populations for more selective therapy, fewer side effects and faster drug development.”

Sloan Kettering yesterday announced it was joining with Quest Diagnostics Inc. (DGX:US), the world’s largest provider of medical testing services, to screen patients’ cancer genes, with an eventual goal of being able to test for 341 genes next year. It will cost $4,000, though Quest said patients will pay less.

“It’s the whole idea of precision medicine -- we’ve been talking about this for 15 or 20 years,” said Jon Cohen, chief medical officer for Madison, New Jersey-based Quest, in a telephone interview. “All of what everybody talked about is finally coming to fruition.”

Drug development based on biomarkers grew from the success scientists found in their research on breast cancer, a disease where tumors often depend on hormones to drive their growth. Researchers determined that they got a better response to therapy by pinpointing the unique biology behind that connection.

“The whole field then blew up when the genome efforts were published,” said José Baselga, Sloan Kettering’s physician in chief, referring to the $2.7 billion Human Genome Project, in which scientists announced in 2003 that they completed sequencing the human genetic code.

Sloan Kettering plans to sequence 10,000 patient tumors a year in what it describes as the biggest such effort in the nation. From that work, it is developing what the center’s researchers refer to as “basket” trials.

Genetic Groupings

Once a tumor’s genes are analyzed, patients will be grouped with others who have the same mutations, with less regard for whether they have colon cancer, lung cancer or melanoma. The drugs they get will be based on that data. Sloan Kettering has 15 basket trials finished or ongoing, three of which will be presented at the oncology meeting this week, Baselga said.

At the Sloan Kettering lab last month, Marc Ladanyi, the hospital’s head of molecular diagnostics, looked over data from a lung tumor just spit out of one of the gene sequencers.

“For people who’ve spent their whole career doing this, it’s like being a kid in a candy shop,” Ladanyi said. “Every batch, you’re seeing stuff that just a few years ago would have been an amazing discovery. Now it’s routine.”

Company Efforts

Companies have joined in as well. Pfizer Inc. and AstraZeneca Plc, are running a joint trial in the U.K. with 200 lung patients to sequence their tumors and try them on 14 different drugs. That’s a change in philosophy from even the very recent past, when researchers were often unable to say why some cancer drugs worked well in some patients but not others.

Amgen (AMGN:US) Inc. started a final-stage trial for its melanoma drug talimogen laherparepvec, or T-Vec, in 2009. The company didn’t look for genetic biomarkers when it picked patients for the experiment. In the 400-patient trial reported last year, 16 percent of patients had their tumors shrink and stay that way for at least six months. It was a success, though a modest one.

Yet of that 16 percent, about two thirds had responses lasting at least a year -- and some longer. Without knowing the genetics of the patients’ tumors, though, Amgen couldn’t understand why. “That was started some time ago, in a little earlier era,” said David Reese, Amgen’s vice president of translational sciences.

Now, the company’s researchers start looking for biomarkers two years before a drug ever gets tested in humans. It’s also going back to do the same for T-Vec.

“Every study we do now has a biomarker component,” Reese said in a telephone interview. “We want to be able to determine which patients are likely to benefit from these therapies.”

FDA Advice

The U.S. Food and Drug Administration has started encouraging companies to look for biomarkers well before they go into human trials, said Richard Pazdur, head of the FDA’s cancer drug unit. He cited Pfizer’s lung cancer drug Xalkori, which has been tied by researchers to a mutation of the ALK gene, which shows up in a tiny percentage of the cancers.

“That’s an example of a drug that never would have been developed,” if researchers hadn’t seen that link, Pazdur said in an interview in Chicago. It’s a treatment that “would have gotten lost in the noise.”

However promising, researchers admit that the field is still in its beginning days.

There may be dozens of mutations to individual cancers, and it could take years to understand them all. So even if hospitals identify certain mutations with new testing programs, they may not be treatable. Also, the same mutation may react differently to treatment, depending on where the tumor is located.

‘Still Early’

“It’s very exciting, but we’re still very early” in figuring how best to take advantage of biomarkers and where the weaknesses may lie, said Dana-Farber’s Anderson.

Biomarker-based drug development grew out of breast cancer, where drugs that targeted a tumor’s dependence on hormones. With the 1977 approval of the estrogen-blocker tamoxifen researchers realized knew that if they could figure out the tumor’s unique biology, they could get a better response to therapy.

Gene-mutation-based trials have taken that specificity to the next level. Sloan Kettering’s experiments could help solve what in the past were often referred to as “miracle” patients from failed trials. For example, in one trial of bladder cancer patients who took Afinitor, researchers gave patients a kidney cancer drug from Novartis AG. (NOVN) Five years later, all but one patient was dead. The living patient, though, was doing well.

‘Perfect Patient’

The researchers couldn’t understand why until they sequenced her tumor and found a mutation called TSC1 that made it particularly sensitive to the medicine.

“She was the perfect patient for that drug, we just didn’t know it,” said David Solit, director of Memorial’s Henry R. Kravis Center for Molecular Oncology, in a telephone interview. “In retrospect, it was obvious.”

The eventual goal is to get drugs to patients faster, said Sloan Kettering’s Baselga. To do that, they’re working with the U.S. Food and Drug Administration to include biomarker research as a key element in drug approvals.

As genetic screening becomes more routine and researchers get access to data, the goal will be to refine old targets and find new ones, said Sloan Kettering’s Charles Sawyers, a researcher looking at what drives tumor growth.

“The ability of the genetics to predict how it might play out if you have the right molecule is amazing,” he said. “We finally understand what we’re doing.”

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