Molecular Pathology Laboratory Network

A targeted therapy for non-small cell lung cancer (NSCLC) created a stir at the 2010 American Society of Clinical Oncology.

Crizotinib, an inhibitor of anaplastic lymphoma kinase, or ALK, demonstrated the ability to shrink tumors in about 90% of patients with advanced disease, according to Yung-Jue Bang, MD, PhD, of Seoul National University in South Korea.

 In a small phase I/II study, the compound produced an objective response in 57% of patients and was well-tolerated. The drug targets a fusion protein -- dubbed EML4-ALK -- which drives tumor growth in up to 5% of all patients with non-small cell lung cancer.

Patients with NSCLC harboring an ALK fusion were recruited into an expanded cohort at the recommended phase II dose within the first-in-patient monotherapy trial. The oral ALK inhibitor, PF-1066, demonstrated a high response rate in patients and was associated with a good safety profile. A phase III study has been initiated.

Bang reported results of 82 patients with advanced disease -- many veterans of up to three previous treatments -- who had the fusion protein. He and colleagues found that the patients had a 72% probability of being progression-free at six months after starting the therapy, and the majority saw their tumors shrink by more than 30%. When the fusion protein was found, the investigators were quickly able to change gears and start the trial.

This study supports the concept of molecular selection of NSCLC patients for appropriately designed treatment.