An expanded Phase I clinical trial finds that the large majority (approximately 90 percent) of patients with advanced non-small cell lung cancer (NSCLC) with a specific form of the ALK responded to treatment with the investigational ALK inhibitor, crizotinib (PF-02341066), and more than half of these patients experienced tumor shrinkage.

"Many of these patients had received three or more prior treatments, and we would expect only about 10 percent to respond," said lead author Yung-Jue Bang, M.D., Ph.D., professor in the Department of Internal Medicine at Seoul National University College of Medicine in Seoul, Korea. "These results are quite dramatic, and represent an important improvement over what we would see with standard chemotherapy for patients with metastatic disease."

When the ALK gene fuses with another gene, it promotes lung cancer cell growth by encoding the production of a tumor-specific protein called anaplastic lymphoma kinase, or ALK -an enzyme that is critical for the growth and development of cancer cells. Crizotinib, which is taken orally, works by inhibiting the ALK enzyme. About one in 20 lung cancer patients in the United States are estimated each year to be diagnosed with ALK-positive NSCLC.

The study assessed crizotinib in patients with NSCLC, most of who had adenocarcinoma and were nonsmokers or former smokers. All of the patients had the ALK gene fusion.

Nearly all patients (87 percent at 8 weeks) who received crizotinib to date responded to this treatment and experienced tumor shrinkage or disease stabilization. Among those, 57 percent had tumor shrinkage. The median duration of treatment was approximately six months. A randomized, Phase III trial (PROFILE-1007) has begun, comparing crizotinib to standard second-line chemotherapy.

Disclosures: Yung-Jue Bang, Consultant or Advisory Role, Pfizer, Honoraria, Pfizer, Research Funding, Pfizer; Eunice Kwak, Research Funding, Pfizer; Alice Shaw, Honoraria, Pfizer, Research Funding, Pfizer; D. Camidge, Research Funding, Pfizer; A. Iafrate, Honoraria, Pfizer, Research Funding, Pfizer; Robert Maki, Research Funding, Pfizer; Benjamin Solomon, Research Funding, Peter MacCallum Cancer Center, Pfizer; Sai-Hong Ou, Research Funding, Pfizer; Ravi Salgia, Research Funding, Pfizer.