Drugs Show Promise for Some Advanced Lung Cancers

Two experimental medications target mutation that fuels treatment resistance

Wednesday, April 29, 2015

WEDNESDAY, April 29, 2015 (HealthDay News) -- Two experimental drugs may help patients whose lung cancer has become resistant to the latest available treatments, separate studies say.

Both drugs showed benefits for patients with advanced lung cancer who develop a particular mutation that makes their tumors resistant to recently approved drugs called EGFR inhibitors.

Currently, little can be done for those patients aside from chemotherapy.

"And those chemotherapy agents don't do a great job," said Dr. Ramaswamy Govindan, an oncologist at Washington University School of Medicine in St. Louis.

The two drugs are not "magic bullets," said Govindan, who wrote an editorial published with the studies in the April 30 issue of the New England Journal of Medicine.

"But in the long struggle against lung cancer, this is a significant step," Govindan said.

Among all people who develop non-small-cell lung cancer -- by far the most common form of lung cancer -- experts say about 12 percent have a mutation in the EGFR gene that fuels their cancer's growth.

In the past couple of years, several drugs have come onto the market that block the flawed gene's activity. They include erlotinib (Tarceva), gefitinib (Iressa), and afatinib (Gilotrif).

Unfortunately, while the drugs often shrink tumors initially, most patients eventually develop resistance to the medications. Most commonly, that's because of a mutation known as T790M, the researchers explained.

Both experimental drugs seem to benefit patients with that mutation.

In one study, researchers tested a drug dubbed AZD9291. They found that of 127 patients with a T790M mutation, 61 percent saw their lung tumors shrink on the treatment.

Most patients went at least six months with no cancer progression, and half went about 10 months or longer. That second figure is similar to what's seen with Tarceva, one of the first-line EGFR inhibitors, said Dr. Pasi Janne, lead researcher on the study.

"So if you give this after a patient becomes resistant (to an EGFR inhibitor), you're doubling the time that they're on a drug that works," said Janne, an oncologist at Dana-Farber Cancer Institute in Boston.

Just as important, he said, the new drug is better tolerated than EGFR medications -- without the potentially severe skin effects of those drugs.

Six percent of patients did have a "serious adverse event" thought to be caused by the medication. But the most common side effects were diarrhea, nausea and rash, which were manageable, Janne said.

"So (the drug) also increases the amount of time that patients have a good quality of life," he said.

Govindan agreed. "Is this a cure? No," he said. "Will it control patients' disease for years? Probably not. But for patients facing the prospect of death, nine or 10 months with no progression is meaningful."

The second study, of an oral drug called rociletinib, had similar results. Of patients with a T790M mutation, 59 percent had their tumors shrink while taking the medication; high blood sugar, diarrhea, nausea and rash were the most common side effects.

The U.S. Food and Drug Administration has fast-tracked AZD9291 for review. If all goes as anticipated, the drug should be available later this year, Janne said.

AstraZeneca, the drug's developer, funded that study, and Janne has served as a consultant to the company.

Neither experimental drug is the answer to battling advanced lung cancer. Janne said patients start developing resistance to AZD9291, too. But researchers are studying other approaches, including using the drug in combination with other treatments.

Another question, Janne said, is whether AZD9291 could be used as an initial therapy for lung cancer driven by EGFR mutations -- rather than waiting until patients develop resistance to EGFR inhibitors.

The broader message for patients, Govindan said, is that advances are being made against a deadly disease.

"Years ago, patients with advanced lung cancer got radiation, then went into hospice," he said.

Chemotherapy improved the picture somewhat, but only about one-third of people with advanced lung cancer see their disease regress with standard chemo, according to the U.S. National Cancer Institute. And even with chemo, patients typically live one year.

SOURCES: Pasi Janne, M.D., Ph.D., director, Lowe Center for Thoracic Oncology, Dana-Farber Cancer Center, Boston; Ramaswamy Govindan, M.D., professor, medicine, Washington University School of Medicine St. Louis; April 30, 2015, New England Journal of Medicine

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