A promising new immunotherapy drug as gained expanded approval from federal regulators for patients whose cancers have a specific genetic signature — the first time a drug has been cleared for use not tied to the site of a tumor.
The U.S. Food and Drug Administration ruling opens the door to redefining cancer, and treatment, not by site — like breast, prostate, or lung cancer — but by the genetic blueprint of the tumor, regardless of where it appears in the body.
The FDA action was also the latest in a long line of landmark approvals for the new drug — pembrolizumab, known as Keytruda — which works by aiding the immune system in attacking tumors. The drug gained notoriety last year after it all but cured former President Jimmy Carter of metastatic skin cancer that had spread to his brain and liver.
The FDA green lighted the drug for expanded use last month after a Johns Hopkins University study found it benefited 86 patients with varying forms of previously-untreatable cancer. All of the patients had specific genetic mutations (targeted by Keytruda) that disrupt the ability of immune-system cells to fix damaged DNA.
Lead researcher Dr. Luis A. Diaz Jr. found that 66 out of the 86 patients had their tumors shrink substantially and stabilize, while 18 among had their tumors vanish completely.
The findings of the clinical trial, published in the journal Science, were so extraordinary that the FDA fast-tracked approval of the drug for wider use.
Officials said the drug can now benefit more 10,000 cancer patients a year, marking a great stride forward in the fight against cancer.
“This is absolutely brilliant,” said Dr. José Baselga, physician in chief at Memorial Sloan Kettering Cancer Center in New York who recent hired Diaz, of the FDA action.
One of study’s participants, Adrienne Skinner, had a form of ampullary cancer so rare that no standard treatments exist for it. Initially, her doctors had recommended surgical removal of parts of her pancreas, small intestine, and gall bladder. But when they found that the cancer had spread to her liver, the surgery was called off.
Then, after a year of unsuccessful chemotherapy treatments, Skinner qualified for Diaz’s clinical trial in April of 2014. Just three months later, in July, all traces of her cancer were gone, and have remained that way until this day.
Usually, cancers are classified by their location in the body: patients are diagnosed with lung cancer, brain cancer, colon cancer, and so on. Conventional cancer therapy has relied primarily on surgery, radiation, and chemo to remove, burn away, or poison tumors, even though those treatments carry significant side effects.
But in recent years, researchers have determined that often what matters most is the genetic mutation that causes the tumors. This has led to new lines of research designed to determine if cancers could be treated or cured with drugs that boost the immune system’s ability to take aim on the mutations, regardless of where the tumors are lodged.
Unfortunately, creating such drugs has proven to be far more complicated than it seemed. Mutations that appear in one type of cancer are rare in others, and treatments for cancers with the same mutation don’t always work for all patients.
But Dr. Drew M. Pardoll, director of the Johns Hopkins Bloomberg-Kimmel Institute, calls the new breed of immunotherapies “a great dream” that is starting to become a reality with drugs like Keytruda.
The Johns Hopkins research grew out of scientists’ determination that the immune system can recognize cancer cells as foreign bodies and destroy them.
Tumors can deflect the immune system's attacks by shielding proteins on their surface — making them imperceptible to the body's natural defenses.
A failed trial of a drug called nivolumab lit the spark for pembrolizumab. Researchers found that the drug prompted one study participant’s immune system to dismantle the tumor’s cloaking mechanism, allowing the patient’s natural defenses to target the foreign proteins on the cancer cells.
Diaz's follow-up research was inspired by this, and he sought patients whose tumors had the same genetic defect, and gave them the drug, known as a “PD-1 blocker.”
The promising results of the trial prompted the FDA to approve the drug for patients with a few types of advanced lung, melanoma, and bladder tumors. A test for the mutations targeted by the drug has also been made available.
Experts believe the advance also opens the door to new approaches to identifying and treating cancer — alongside surgery, radiation, and chemo — that aim to boost the body’s natural immune defenses to fight off cancer.
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