Crizotinib shows early promise as treatment for ALK+ NSCLC

Crizotinib, an investigational drug, demonstrated an association with a sharp increase in survival rates for patients with advanced non-small cell lung cancer (NSCLC) with an anaplastic lymphoma kinase (ALK) positive genetic alteration, according to the results of an early-phase study presented at the 2011 annual meeting of the American Society of Clinical Oncology.

To determine the impact of crizotinib on overall survival of patients with ALK+ NSCLC, researchers examined survival of 82 ALK-positive patients who enrolled in the expansion cohort of the phase 1 trial of crizotinib. Thirty-seven NSCLC ALK-positive patients from phase 1 sites who were not treated with crizotinib (ALK-positive controls) and 253 NSCLC ALK/epidermal growth factor receptor patients from 1 site (ALK- controls) were identified as comparators.

One-year overall survival for the 82 ALK-positive patients treated with crizotinib was 77% and 2-year overall survival was 64%. Among the 37 ALK-positive controls, 1-year overall survival was 73%; while 2-year overall survival was 33%.

Additional studies presented at the meeting also looked at efficacy, safety, and tolerability of the drug. A continuation of the study above reported updated safety and response data and preliminary progression free survival data, finding that the efficacy of crizotinib in patients with ALK-positive NSCLC was “robust, rapid, durable and clinically meaningful.” The most common adverse events included vision disorder and gastrointestinal events, such as nausea, diarrhea, and vomiting. These adverse effects typically had early onset and diminished as the treatment continued.

In another ongoing study 83% of patients had target lesion shrinkage, while 54% had their tumors shrink by 30% or more. The most frequent treatment-related adverse events were mild and included nausea, vision disorder, vomiting, and diarrhea; however 2 of 9 deaths during the study were considered treatment related. Researchers concluded that crizotinib was safe and well-tolerated, and preliminary evidence indicated improved symptoms and clinically meaningful antitumor activity.

Pfizer announced last month that it filed a new drug application with FDA for approval of crizotinib in patients with advanced NSCLC whose tumors express the EML4-ALK fusion oncogene. FDA has granted the drug fast-track designation.

With regard to the expansion cohort phase 1 trial that enrolled the 82 ALK-positive patients, Alice Shaw, MD, PhD of the Massachusetts General Hospital Cancer Center and an author of the findings was quoted as saying in the NCI Cancer Bulletin: “This trial confirms what we have known from the very first patient-that this drug is a great option for these patients.” She added that little is known about the natural history of this particular type of lung cancer and additional research is needed, according to the online publication.