June 2, 2015 / 5:30 AM / 4 years ago

Transition to gene-based cancer treatment may not be simple

CHICAGO (Reuters) - The medical view of cancer is in transition, as cancer doctors increasingly focus on the defective genes that are driving the disease rather than the organ in which it takes root.

Oncologists hope that by understanding the genetic underpinnings of cancer rather than focusing on whether it originated in the breast or the liver, they will be able to give patients better, more personalized and more effective treatments.

But leading cancer experts say that as doctors have tested that theory more closely, they are seeing both successes and failures, suggesting that the ideal route to treating cancer may be far more complicated than hoped.

At the moment, there is not enough understanding of the mutations that drive cancer growth, said Dr. Richard Pazdur, chief of oncology at the U.S. Food and Drug Administration

    “What people want and the scientific reality are two different situations,” Pazdur said in an interview at the American Society of Clinical Oncology (ASCO) meeting in Chicago.

    He said there are currently “only a handful of therapies” that target specific cancer-causing genes. Some oncologists have begun using those drugs to treat cancers in people with the corresponding genetic mutations, even when the drugs haven’t been approved for the type of cancer a patient has.

    When the drugs work, the results are dramatic. Tumors seem to melt away, and advances in survival are counted in months and years, not weeks. The transformation has led many doctors to question whether the current practice of approving drugs based on the organ they target needs to change.

    But there have also been disappointments. Drugs made by Roche and GlaxoSmithKline that target cancers with a mutation known as BRAF can have a powerful, albeit transient, effect in beating back the deadly skin cancer melanoma. These drugs do not work, however, in patients with colon cancers driven by the same BRAF mutation, according to a 2012 study that began to sow doubt among some experts.  

“The temptation in practice is to get the tumor sequenced, and if something comes up for which there is an approved drug, your clinician is tempted to try that, no matter what the tumor is. But it might not be that simple,” said Dr. Barbara Conley of the National Cancer Institute.

    As it turns out, colon cancers with BRAF mutations have another driver mutation called EGFR. In those tumors, doctors may need to use a combination of agents that hit both targets, , according to new data presented at ASCO this weekend.

Dr. Bert Vogelstein, a cancer geneticist at Johns Hopkins University in Baltimore, said there is scant evidence that matching a patient’s mutation to a targeted drug improves care.

    “It’s definitely an unproven assumption and we ought to test it,” Vogelstein said.

    JUMP IN GENETIC PROFILING

    Oncologists interviewed by Reuters said genetic profiling of tumors is becoming much more routine, particularly if a patient with advanced disease hasn’t recovered with more traditional approaches. Foundation Medicine Inc, which makes genetic profiling tests, has seen clinical demand for its tests jump 67 percent in the first quarter from the same period a year ago.

    Dr. Richard Schilsky, chief medical officer of ASCO and a University of Chicago Medicine oncologist, estimates that in up to 70 percent of such tests, doctors find a genetic mutation that can be matched with a drug. Insurers, however, aren’t quick to cover a treatment for an unapproved use unless there is evidence that it will work.

“They are experimenting. It’s not like these therapies don’t have harms as well. They have side effects,” said Jennifer Malin, medical director for cancer drugs at health insurer Anthem Inc.

    The issue will be studied more broadly in a large cancer clinical trial launched by the NCI. It is designed to match the underlying genetic defect driving a person’s tumor with one or more of 20 approved or experimental drugs targeting that gene.

    ASCO is also starting a clinical trial to gather data on how patients fare when doctors order genetic profiles and use the data to influence treatment. The TAPUR trial will allow these patients to be treated with one of five FDA-approved drugs provided for free, and their data will be collected to help answer this question.

    Early results from a small Foundation Medicine-sponsored trial presented on Sunday showed a limited benefit. Researchers at University of Texas MD Anderson Cancer Center tested 339 patients with very advanced cancers. For 122 patients, the team was able to match the genetic defects in their tumors to a drug or combination of drugs targeting those defects. They also followed 66 patients whose cancers were not matched to a targeted drug.

    The patients whose tumors were matched with a targeted drug lived 2 months longer than the unmatched patients. Dr. Jennifer Wheler of MD Anderson, who led the study, thinks the outcome might improve if the approach were tried in healthier patients.

But it will take large clinical studies to prove the hypothesis that picking a patient’s therapy based on the mutation in his or her tumor works. “It’s like everything else. The devil is in the details,” Vogelstein said.

Editing by Michele Gershberg and Sue Horton

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