On April 18, the U.S. Food and Drug Administration (FDA) approved the tyrosine kinase inhibitor alectinib (Alecensa) for adjuvant treatment after tumor resection in patients with ALK-positive non–small cell lung cancer (NSCLC), as detected by an FDA-approved test. Alectinib is an orally bioavailable inhibitor of ALK and RET proteins.
ALINA Trial
Efficacy was demonstrated in a global, randomized, open-label trial (ALINA, ClinicalTrials.gov identifier NCT03456076) in patients with ALK-positive NSCLC who had complete tumor resection. Eligible patients were required to have resectable stage IB to IIIA NSCLC (by American Joint Committee on Cancer, 7th edition) with ALK rearrangements identified by a locally performed FDA-approved ALK test or by a centrally performed Ventana ALK (D5F3) CDx assay. A total of 257 patients were randomly assigned (1:1) to receive alectinib at 600 mg orally twice daily or platinum-based chemotherapy after tumor resection.
The major efficacy outcome measures were disease-free survival in the subgroup of patients with stage II to IIIA NSCLC and disease-free survival in the overall study population (stage IB–IIIA), as assessed by investigator. In patients with stage II to IIIA NSCLC, median disease-free survival was not reached (95% confidence interval [CI] = not estimable to not estimable) in the alectinib arm and 44.4 months (95% CI = 27.8 months to not estimable) in the chemotherapy arm (hazard ratio [HR] = 0.24; 95% CI = 0.13–0.45; P < .0001). Similar results were seen in the overall study population, with median disease-free survival not reached (95% CI = not estimable to not estimable) in the alectinib arm and 41.3 months (95% CI = 28.5 months to not estimable) in the chemotherapy arm (HR = 0.24; 95% CI = 0.13–0.43; P < .0001).
The most common (≥ 20%) adverse reactions in patients taking alectinib were hepatotoxicity, constipation, myalgia, COVID-19 infection, fatigue, rash, and cough.
Dosing and Regulatory Approval Information
The recommended dose of alectinib is 600 mg orally twice daily with food for 2 years or until disease recurrence or unacceptable toxicity.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence; the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application; and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was granted Priority Review and Orphan Drug designation, and the FDA approved it 1 month ahead of the FDA goal date.
