Alectinib for ALK-Positive NSCLC Approved

In less than 3 months of being granted priority review, Roche’s anaplastic lymphoma kinase (ALK) inhibitor alectinib (Alecensa) has been approved for patients with advanced ALK-positive non-small cell lung cancer (NSCLC) whose disease has progressed or who cannot tolerate crizotinib (Xalkori).

Today’s approval was based on the results of 2 phase 2 studies. One was a single-arm, open-label, multicenter trial (NP28761) evaluating the safety and efficacy of alectinib in 87 people with ALK-positive NSCLC whose disease progressed on crizotinib. Nearly 50% of trial participants saw their tumor shrink. Those with metastases to the brain or other regions of the central nervous system (CNS) also saw their cancer respond to alectinib, indicating that the drug crosses the blood-brain-barrier, a lipid-rich region which is usually difficult to penetrate. The duration of primary tumor response was sustained for a median period of 7.5 months.

A second trial (NP28673) evaluated the safety and efficacy of alectinib in 138 individuals with a similar profile as in NP28761. Using RECIST criteria, a 50% response rate was observed with respect to tumor shrinkage in this population. While the median duration of response was longer in this group (11.2 months), a CNS response in those with brain and other CNS metastases was observed. Between the 2 trials, 61% of participants who had measurable brain metastases experienced a complete or partial reduction in their brain tumors, lasting an average of 9.1 months.

The most common side effects of Alecensa are fatigue, constipation, edema, and myalgia. Alecensa may cause serious side effects, including liver problems, severe or life-threatening inflammation of the lungs, very slow heartbeats and severe muscle problems. Treatment with Alecensa may cause sunburn when patients are exposed to sunlight.

Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research said, “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. 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.”