August 19, 2015 / 9:30 PM / 5 years ago

First trial targeting mutation, not cancer type, gives mixed results

(Reuters Health) - A powerful skin cancer drug may also be effective against lung cancer and other types of malignancies, according to a novel study that focused on a gene mutation seen in many kinds of tumors.

This sort of study is “the new wave,” said Dr. Otis Brawley, chief medical officer of the American Cancer Society, who wasn’t involved in the research. “This is the new molecular medicine,” he told Reuters Health.

Most cancer drug studies focus on a particular type of malignancy. But projects in recent years to analyze the DNA of various cancer types have found that certain gene mutations appear in many kinds of tumor, and appear to play a role in driving the disease.

In the new study, researchers focused on a mutation known as BRAF V600, which is a defect in a genetic instruction that tells a cell when to die. It is most common in metastatic melanoma, but other tumors harbor it as well.

The goal was to see if the drug vemurafenib, already approved for metastatic melanoma cases with the BRAF mutation, would work in other tumors with the same mutation.

Among 20 patients with non-small-cell lung cancer, the most common form of lung cancer, 42 percent of patients showed signs of responding to the drug and average progression-free survival time was 7.3 months, researchers reported in The New England Journal of Medicine.

The response rate was 43 percent among 18 people with either Erdheim-Chester disease or Langerhans’-cell histiocytosis, both rare cancer-like conditions.

Other cancers with the BRAF V600 mutation showed a far more tepid response to the drug, sold in tablet form under the brand name Zelboraf by F. Hoffmann-La Roche and Genentech. The companies paid for the trial.

Similar studies are in the pipeline and could change the way cancer is treated, Brawley said.

“It’s not whether you have pancreatic cancer, or colon cancer or lung cancer that’s going to be important to the treating clinician,” he said. “What’s going to be important to the treating clinician is what’s wrong with your tumor at a molecular level.”

The new research is “a proof-of-concept kind of study,” he said. “We are going to see more and more things like this - someone with colon cancer who didn’t do well with the normal treatment may get their tumor analyzed and (one) of these small molecule drugs the FDA has approved for some other cancer might be tried” because it shares a similar genetic defect.

Despite the new trial’s encouraging results in lung cancer and two other tumors, much smaller effects, or no effects, were seen in patients with colorectal cancer, brain tumors, multiple myeloma, anaplastic thyroid cancer or bile duct cancer.

“It’s a starting point,” said the study’s lead author Dr. David Hyman, acting director of developmental therapeutics at Memorial Sloan Kettering Cancer Center in New York. “It’s harder to draw firm conclusions about the effectiveness of vemurafenib in these patients.”

In the cancer types with less response, Hyman noted, the BRAF V600 mutation is typically present in fewer than 5 percent of tumors that have resisted conventional therapy and spread, so only those patients would be candidates for the drug.

The treatment costs about $11,000 to $12,000 per month.

In a commentary in the Journal, Dr. David Hunter of the Harvard T.H. Chan School of Public Health and Dr. Ralph D’Agostino Sr. of Boston University caution that newer sequencing studies have found that individual tumors can be very heterogeneous. Different parts of the same primary tumor may have very different groups of mutations, which would further complicate treatment with targeted drugs.

Such drugs may block one chemical pathway used by cancer cells to grow and spread, but “if you block one route, (a tumor) can always detour around it,” which is why the benefits of vemurafenib didn’t always last, Brawley said.

“It’s only a matter of time before these tumors find a way around that blockage, some faster than others,” he said. “But they’re demonstrating they can block it, and that this drug, already approved in melanoma, has some usage in several of these diseases.”

SOURCE: New England Journal of Medicine, online August 19, 2015.

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