ASCO 2013 Report – Advanced lung cancer with dysfunctional ALK gene responds to targeted therapy

by Bruce Sylvester – Patients with an advanced kind of lung cancer and a dysfunctional ALK gene have achieved better outcomes with the targeted investigative therapy crizotinib rather than with standard chemotherapy, researchers reported on June 1, 2013 at ASCO. The findings were also published online on June 1 in the New England Journal of Medicine.

Crizotinib acts directly on the abnormal ALK gene. Crizotinib hits key enzymes within cells called kinases, which are often abnormal in cancer. Originally designed to block a kinase called MET, the drug also blocks ALK.

“This study demonstrates the value of testing lung cancer tissue for an ALK rearrangement, and it underscores the potential of cancer genomics to target cancer treatments to each patient,” said senior author, Pasi A. Jänne, MD, PhD, director of the Lowe Center for Thoracic Oncology of Dana-Farber Cancer Institute in Boston. “ALK now becomes the second abnormal gene [after EGRF] that we are able to successfully target in lung cancer with drugs other than chemotherapy.” The lead author of the study is Alice Shaw, MD, PhD, of Massachusetts General Hospital in Boston.

Lung cancers with the first identified dysfunctional gene, EGFR, are now often treated with EGFR inhibitors prior to chemotherapy.

The phase 3 trial investigators enrolled 347 patients with advanced or metastatic NSCLC who had already been treated with standard chemotherapy. The most common side effects associated with crizotinib therapy – visual disorders, gastrointestinal problems, elevated liver enzymes, and leg swelling – were generally mild, Dr. Jänne said, and less severe than the fatigue and hair loss associated with chemotherapy.

Patients with non-small cell lung cancer and an abnormal ALK gene in their tumor cells who were treated with crizotinib achieved a median of 7.7 months before disease progression, compared with 3 months for those who received traditional chemotherapy. Crizotinib subjects also achieved better quality of life outcomes.

The authors noted that NSCLC is the most common form of lung cancer, and an abnormal ALK is found in about 5 percent of NSCLC cases.

Support for the study was provided by Pfizer, Inc.