Alectinib: A Review in Advanced, ALK-Positive NSCLC

Area of Science:

• Oncology
• Pharmacology
• Clinical Trials

Background:

• Alectinib (Alecensa) is a selective anaplastic lymphoma kinase (ALK) inhibitor.
• It is approved for advanced ALK-positive non-small cell lung cancer (NSCLC) in the EU and USA.
• Recommended dosage is 600 mg twice daily.

Purpose of the Study:

• To evaluate the efficacy and safety of alectinib in advanced ALK-positive NSCLC.
• To compare alectinib with crizotinib as first-line therapy.
• To assess alectinib's effectiveness in patients previously treated with crizotinib and chemotherapy.

Main Methods:

• Phase III studies (ALEX, ALUR) compared alectinib to crizotinib or chemotherapy.
• Phase II studies (NP28673, NP28761) assessed alectinib in previously treated patients.
• Outcomes included progression-free survival (PFS), objective response rates (ORRs), and central nervous system (CNS) events.

Main Results:

• Alectinib significantly improved PFS versus crizotinib in first-line therapy (ALEX study).
• Alectinib demonstrated superior PFS compared to chemotherapy in previously treated patients (ALUR study).
• Significant improvements in CNS-related outcomes and manageable tolerability with mostly mild-to-moderate adverse events (AEs) were observed.

Conclusions:

• Alectinib is an effective treatment for advanced ALK-positive NSCLC in both first-line and previously treated settings.
• Its efficacy, particularly CNS benefits, and favorable tolerability profile support its use.
• Current guidelines recommend alectinib, with NCCN guidelines favoring it for first-line therapy.