Patients with advanced lung cancer who carry an abnormal gene appear to fare better when treated with targeted therapy than with traditional chemotherapy, according to a study published in the New England Journal of Medicine.
In a trial of patients with non-small cell lung cancer (NSCLC) whose tumors had an abnormal ALK gene, those who were treated with the targeted therapy oral crizotinib (which acts directly on ALK) did not experience a worsening of their disease for a median of 7.7 months versus 3 months for patients who received standard chemotherapy. The patients treated with crizotinib also had a better quality of life.
The results of the study demonstrate the value of testing lung cancer tissue for an ALK gene rearrangement, according to senior author Pasi A. Jänne, MD, PhD, director of the Lowe Center for Thoracic Oncology at the Dana-Farber Cancer Institute in Boston, Massachusetts. He adds that ALK is the second abnormal gene that can be targeted in patients with lung cancer with drugs other than chemotherapy. The first gene was epidermal growth factor receptor (EGFR), which is now commonly treated with EGFR inhibitors before patients are treated with chemotherapy.
The phase 3 trial involved 347 patients with advanced or metastatic NSCLC who previously had been treated with standard chemotherapy. The side effects associated with crizotinib were generally mild, and included visual disorders, gastrointestinal problems, elevated liver enzymes, and leg swelling.
NSCLC is the most common form of lung cancer. Abnormal ALK is present in only approximately 5% of patients with NSCLC, but that translates to about 5000 new patients each year who may benefit from crizotinib therapy, the researchers said.
Crizotinib targets key enzymes within kinase cells, which are often abnormal in individuals with cancer. It was originally designed to block a kinase called MET but was later discovered to also target ALK. The ALK abnormality in NSCLC is not a mutation but, rather, the result of a chromosomal rearrangement, in which the structure of the chromosome is altered.