Genetic Screening Helps Get Target Drugs to Lung Cancer Patients

During the last decade there has been an explosion of knowledge about what cancer is and how it can be treated. As a result, scientists have developed new drugs known as targeted molecular therapies designed to zero in on the mechanisms that supply blood to tumors and promote their growth and division, which spares healthy tissue, causes fewer side effects, and improves quality of life. These drugs have been studied in clinical trials over a number of years and some have been approved by the FDA and are available for use. The challenge is to match the best treatment—chemotherapy, radiation, targeted therapies or a combination—to the patient, which two recent studies suggest could easily be accomplished with screening tests that look for specific genetic or molecular characteristics.

Both studies involved patients with non-small cell lung cancer, the most common lung cancers, accounting for about 80 percent of all lung cancers. In one, Dr. Masahiro Fukuoka of Kinki University in Osaka, Japan, and Dr. Tony Mok of the Chinese University of Hong Kong and colleagues analyzed data on 261 East Asians whose tumors had specific mutations in genes for the epidermal growth factor receptor (EGFR), which reside on the surface of cells and take messages ordering the cells to grow and divide. The patients had been nonsmokers or light smokers.

Nearly 25 percent who had the EGFR mutations and who took AstraZeneca’s target drug Iressa, or gefitinib, survived a year without their cancer progressing, compared to 6.7 percent who received chemotherapy. “Overall, patients who got gefitinib had a longer time from the start of treatment to the worsening of disease,” said Dr. George Simon, director of thoracic oncology at Fox Chase Cancer Center in Philadelphia. “And it appeared that the drug’s benefit was primarily seen in patients with EGFR mutations.”

In another study, a team lead by Dr. Rafael Rosell of the Catalan Institute of Oncology in Spain screened 2,105 people with non-small cell lung cancer for EGFR mutations. Those with the mutations were put on Roche’s Tarceva, or erlotinib. They survived an average of 14 months without progression of their disease and 27 months overall, more than twice as long as the rates seen in other treatment groups. “Screening for EGFR mutations is warranted in women with lung cancer, in those who have never smoked, and in those with non-squamous tumors. Large-scale screening of patients for EGFR mutations, with subsequent customization of erlotinib, is feasible and improves the outcome,” Rosell and colleagues conclude.

“This basically confirmed what we have thought, that in selected populations (light smokers or those who never smoked), those testing positive for EGFR mutations will do much better in progression-free survival than if you put the patient on chemo,” said Dr. Edgardo Santos, an assistant professor of medicine in the hematology and oncology section at the University of Miami’s Sylvester Comprehensive Cancer Center. “For the first time in a selected population, you have a drug which can compete with systemic chemotherapy—there is a pill that matches systemic chemotherapy.”

“The evidence is building that there is potentially a particular benefit for the group of people who have EGFR mutations,” said Charlotte Arnold, a spokeswoman for Genentech, which is now owned by Roche. She said Roche is conducting a late-stage study in Europe to determine the effectiveness of Tarceva as a first-line treatment for lung cancer patients with EGFR mutations. The study incorporates the use of a companion diagnostic test.

In an editorial, Dr. Adi Gazdar of the University of Texas Southwestern Medical Center in Dallas said the studies “suggest that first line (EGFR) tyrosine kinase therapy should be considered for carefully selected subgroups of patients of East Asian and non-East Asian origin who have nonsmall-cell lung cancer.” He added that “inhibition of EGFR signaling, the poster child for personalized medicine, presents multiple opportunities for testing a wealth of targeted therapies.”

Both studies are published in the New England Journal of Medicine.