FDA Approves Alectinib for ALK-Positive NSCLC

On December 11, 2015, the US Food and Drug Administration (FDA) approved alectinib (Alecensa, Genentech) for patients with ALK-rearrangement positive non-small cell lung cancer (NSCLC) that is refractory to another ALK-targeted oral drug, crizotinib (Xalkori, Pfizer).

About 5% of patients with NSCLC harbor tumors with an ALK rearrangement. The FDA approved the first ALK-positive targeted drug, crizotinib, in 2011.

"Today’s approval provides a new therapy for a group of patients who would have few treatment options once their disease no longer responds to treatment with Xalkori,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research in a statement. "In addition to the primary effect on tumors in the lung, Alecensa clinical trials provide evidence of an effect on tumors that had spread to the brain, which is an important effect for clinicians to understand."

The indication of alectinib is similar to that of another ALK-targeted agent approved by the FDA last year, ceritinib (Zykadia, Novartis), also for those patients refractory to crizotinib.

Alectinib was granted approval through the FDA’s accelerated approval regulatory pathway. Alectinib had also received an FDA Breakthrough Therapy designation and an orphan drug designation.

The trial results supporting the approval were two single-arm, phase II studies of patients with ALK-positive NSCLC whose tumors no longer responded or could no longer be controlled by crizotinib therapy. Oral alectinib was given as a 600 mg dose twice daily.

In a global study of 138 patients, 44% of patients had a partial response that lasted for an average of 11.2 months. In a second North American study of 87 patients, 38% of patients had partial tumor shrinkage that lasted for an average of 7.5 months.

Both trials also measured the drug’s activity on brain metastases-a common site of ALK-positive NSCLC spread. Sixty-one percent of patients on both trials who had detectable brain metastases had a complete or partial reduction in their brain tumors that lasted an average of 9.1 months. 

The most common side effects of alectinib were fatigue, constipation, edema, and myalgia. The drug can cause serious side effects, including liver abnormalities, severe or life-threatening inflammation of the lungs, bradycardia, and severe muscle problems, and can also cause sunburn when patients are exposed to sunlight.

Alectinib is currently being tested as a first-line therapy for metastatic ALK-positive NSCLC in a global, randomized phase III study that compares alectinib with crizotinib.