Alectinib Granted Priority Review for First-Line Treatment of ALK-Positive Lung Cancer

An approval decision for Alecensa is expected by November 30, 2017.

The FDA today granted Priority Review for alectinib (Alecensa) as a first-line treatment for patients with anaplastic lymphoma kinase (ALK)-positive, locally advanced, or metastatic non-small cell lung cancer (NSCLC)

The supplemental New Drug Application for alectinib was based on findings from the phase 3 ALEX and J-ALEX studies, which were presented at the American Society of Clinical Oncology annual meeting.

The randomized, multicenter, open-label ALEX study evaluated the safety and efficacy of alectinib compared with crizotinib in treatment-naïve patients with ALK-positive NSCLC whose tumors were characterized by the VENTANA ALK CDx Assay, according to a press release.

During the study, 303 participants across 161 sites in 31 countries were randomized to receive either alectinib or crizotinib. The results of the study showed alectinib improved progression-free survival (PFS) 53% compared with crizotinib.

The median PFS was not yet reached in the alectinib arm versus 11.1 months in the crizotinib arm, according to the release.

An independent review committee reported median PFS was 25.7 months in the alectinib compared with 10.4 months in the crizotinib arm.

Compared with crizotinib, alectinib reduced the risk of central nervous system (CNS) progression by 84%. The 12-month cumulative rate of CNS progression in patients with or without existing CNS metastases at baseline was 9.4% for the alectinib arm and 41.4% for the crizotinib arm, according to the report.

Data for overall survival are currently immature, with only a quarter of events reported.

Grade 3 to 5 adverse events (AEs) were less frequent in patients who received alectinib compared with crizotinib. The most common AEs were alanine transferase and aspartate transferase, and anemia. AEs that resulted in discontinuation, dose reduction, and dose interruption were lower in the alectinib arm.

The randomized, open-label J-ALEX study was designed to compare the safety and efficacy of alectinib with crizotinib in Japanese patients. A total of 207 individuals with ALK-positive, advanced or recurrent NSCLC, who had not been treated with an ALK inhibitor were enrolled in the study.

The results showed alectinib reduced the risk of PFS by 62% compared with crizotinib. The median PFS was 25.9 months among patients in the alectinib arm versus 10.2 months in the crizotinib arm.

The risk of CNS progression was reduced by 81% in patients in the alectinib arm who did not have brain metastases at baseline. Among patients with brain metastases at baseline, alectinib reduced the risk of CNS progression by 49%.

Grade 3 to 4 AEs were less frequent in the alectinib arm compared with the crizotinib arm. The most common AEs were an increase in muscle enzymes and interstitial lung disease. AEs leading to discontinuation and dose interruption were reported to be lower in the alectinib arm compared with the crizotinib arm.

“Phase 3 results showed Alecensa reduced the risk of disease worsening by more than half compared to the current standard of care and lowered the risk of tumors spreading to or growing in the brain by more than 80%,” Sandra Horning, MD, chief medical officer and head of Global Product Development at Genentech, said in the release. “We are working closely with the FDA to bring this medicine as an initial treatment for people with ALK-positive NSCLC as soon as possible.”

A decision on approval by the FDA is expected by November 30, 2017.