Potential new drug therapies targeting genetic mutations benefit lung-cancer patients

Some lung-cancer patients at UT Southwestern Medical Center are responding well to potential new drug therapies targeting genetic mutations. Their participation in a national study is helping to forge new avenues to attack the disease.

"For those people who have mutations, a drug that could target this cancer-specific vulnerability should be very impactful," said Dr. Joan Schiller, chief of hematology/oncology at UT Southwestern and deputy director of the Harold C. Simmons Cancer Center, the only National Cancer Institute-designated cancer center in North Texas. "These patients can have major responses with a lot less toxicity. It's very exciting."

At UT Southwestern, erlotinib and four other mutation-targeting drugs still in clinical trials are available to patients whose lung-cancer tumors are being examined for mutations. Some of the 40 UT Southwestern patients enrolled in the study have benefited from these drugs, said Dr. Schiller, one of the authors of a multi-institutional study released at the American Society of Clinical Oncology's recent annual meeting.

Study author Dr. John Minna, director of the Nancy B. and Jake L. Hamon Center for Therapeutic Oncology and the W.A. "Tex" and Deborah Moncrief Jr. Center for Cancer Genetics, said, "With regular chemotherapy, maybe 20 percent to 30 percent of advanced lung-cancer patients will see shrinkage of their cancer. For patients with a mutation who get treated with a targeted drug, it can be 70 percent. These are usually very dramatic responses."

In all, more than half of advanced lung-cancer patients participating in the 14-center national study were found to have acquired genetic mutations in their cancer, a surprisingly high ratio to researchers but potentially goods news that could lead to more mutation-targeted drug treatments.

Lung cancer kills nearly 160,000 people per year. The survival rate is poor for those with late-stage disease, but with targeted treatments that rate improves significantly.

Researchers are analyzing the tumors of advanced lung-cancer patients for "cancer-driver gene" mutations, which have become effective therapeutic targets to combat the disease. The trial's facilities are taking part in the National Cancer Institute-sponsored U.S. Lung Cancer Mutation Consortium study, which has enrolled more than 1,000 patients since its start in early 2010.

The study showed at least one cancer-causing mutation in 280 of 516 tumor samples examined nationally thus far. Participants with mutations were slightly older, with a median age of 62 as compared to 59 for the patients without such alterations. Gender and smoking history were not associated with mutation status.

For lung-cancer patients whose tumor mutations are either unknown or not tested, traditional chemotherapy is the usual course of treatment. Of 10 known mutations that drive lung cancer, drugs are being tested to target five. For a sixth mutation, erlotinib has gained Food and Drug Administration approval.

Dr. Schiller said lung cancer tumor testing could one day become routine, leading to more effective, targeted drug therapies and a better cure rate for the disease.

"We don't have a lot of drugs for the mutations now, and we have even fewer drugs for the resistant mutations. It's all a very new field," Dr. Schiller said.

The ongoing study is led by the Dana-Farber Cancer Institute in Boston and was supported by funding from the National Cancer Institute.