On April 18, 2024, the ALK inhibitor alectinib was approved by the U.S. Food and Drug Administration (FDA) for adjuvant treatment after tumor resection in patients with ALK-positive non–small cell lung cancer (NSCLC), as detected by an FDA-approved test.1
Supporting Efficacy Data
Approval was based on findings in the global open-label -ALINA trial (ClinicalTrials.gov identifier NCT03456076). In this study, 257 patients with completely resected stage IB (tumors ≥ 4 cm) to IIIA disease were randomly assigned to receive oral alectinib at 600 mg twice daily or platinum-based chemotherapy.
OF NOTE
Alectinib has warnings/precautions for hepatotoxicity, interstitial lung disease/pneumonitis, renal impairment, bradycardia, severe myalgia and creatine phosphokinase elevation, hemolytic anemia, and embryofetal toxicity.
Among patients with stage II to IIIA disease, investigator--assessed median disease-free survival was not reached (95% confidence interval [CI] = not estimable to not estimable) in the alectinib group vs 44.4 months (95% CI = 27.8 months to not estimable) in the chemotherapy group (hazard ratio [HR] = 0.24, 95% CI = 0.13–0.45, P < .0001).
Among all patients—ie, including those with stage IB disease—median disease-free survival was not reached (95% CI = not estimable to not estimable) in the alectinib group vs 41.3 months (95% CI = 28.5 months to not estimable) in the chemotherapy group (HR = 0.24, 95% CI = 0.13–0.43, P < .0001).
How It Is Used
The recommended alectinib dose is 600 mg twice daily with food for 2 years or until recurrence or unacceptable toxicity. Product labeling provides information on dosage modification, including dose reduction, for adverse reactions including alanine transaminase (ALT) or aspartate transaminase elevation, bilirubin elevation, interstitial lung disease/pneumonitis, renal impairment, bradycardia, creatine phosphokinase (CPK) elevation, and hemolytic anemia. The recommended starting dose in patients with severe hepatic impairment is 450 mg twice daily.
Safety Profile
In the ALINA trial, the most common adverse events of any grade in the alectinib group were hepatotoxicity (61% vs 13% in the chemotherapy group), constipation (42% vs 25%), myalgia (34% vs 2%), COVID-19 infection (29% vs 1%), fatigue (25% vs 28%), rash (23% vs 10%), and cough (20% vs 3%). The most common grade 3 or 4 adverse events in the alectinib group were hepatotoxicity (5%) and rash (2%). The most common grade 3 or 4 laboratory abnormalities were increased CPK (8%), increased bilirubin (2%), and increased ALT (2%).
KEY POINTS
- Alectinib was approved by the U.S. Food and Drug Administration (FDA) for adjuvant treatment after tumor resection in patients with ALK-positive NSCLC, as detected by an FDA-approved test.
- The recommended alectinib dose is 600 mg twice daily with food for 2 years or until recurrence or unacceptable toxicity.
Serious adverse events occurred in 13% of the alectinib group, most commonly pneumonia (3.9%), appendicitis (3.1%), and acute myocardial infarction (1.6%). Adverse events led to treatment discontinuation in 5%, most commonly (≥ 1%) pneumonitis and hepatotoxicity.
Alectinib has warnings/precautions for hepatotoxicity, interstitial lung disease/pneumonitis, renal impairment, bradycardia, severe myalgia and CPK elevation, hemolytic anemia, and embryofetal toxicity. Patients should be advised not to breastfeed while receiving alectinib.
REFERENCE
1. U.S. Food and Drug Administration: FDA approves alectinib as adjuvant treatment for ALK-positive non-small cell lung cancer, April 18, 2024. Available at https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-alectinib-adjuvant-treatment-alk-positive-non-small-cell-lung-cancer. Accessed May 1, 2024.
