ALEX Trial: Alectinib versus Crizotinib in Treatment-Naïve Advanced ALK-Positive NSCLC

2020 Year in Review: Non–Small-Cell Lung Cancer —February 6, 2021


Lung Cancer

Researchers presented updated 5-year progression-free survival and overall survival data from a clinical trial evaluating the efficacy and safety of alectinib versus crizotinib in previously untreated patients with ALK-positive NSCLC.

Alectinib is a next-generation oral anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) that has demonstrated promising activity in the treatment of patients with ALK-positive non–small-cell lung cancer (NSCLC). ALEX is a global, randomized phase 3 trial evaluating the efficacy and safety of alectinib versus crizotinib in treatment-naïve patients with ALK-positive NSCLC. Study results at the primary data cutoff (February 9, 2017) showed significant improvement in progression-free survival (PFS) with alectinib compared with crizotinib. Researchers reported the updated 5-year PFS and overall survival (OS) data from the ALEX trial during the ESMO Virtual Congress 2020.

A total of 303 patients aged ≥18 years with untreated, stage IIIB/IV ALK-positive NSCLC and an Eastern Cooperative Oncology Group performance score of 0 to 2 were randomized to receive either alectinib 600 mg twice daily (N = 152) or crizotinib 250 mg twice daily (N = 151) until progressive disease, toxicity, withdrawal, or death. The primary end point was investigator-assessed PFS, and secondary end points included PFS as assessed by an independent review committee, objective response rate, OS, and safety.

The median duration of follow-up for investigator-assessed PFS was 48.2 months (range, 0.5-62.7 months) in the alectinib arm and 23.3 months (range, 0.3-60.6 months) in the crizotinib arm. Mature data demonstrated a significant improvement in median PFS with alectinib versus crizotinib (34.8 vs 10.9 months; stratified hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.32-0.58). The median duration of follow-up for OS was 48.2 months (range, 0.5-62.7 months) in the alectinib arm and 23.3 months (range, 0.3-60.6 months) in the crizotinib arm. The OS data remain immature, with 37% of events recorded. The median OS had not yet been reached with alectinib and was 57.4 months with crizotinib (stratified HR, 0.67; 95% CI, 0.46-0.98). The 5-year OS rate was 62.5% with alectinib versus 45.5% with crizotinib. At the time of analysis, 34.9% of patients in the alectinib arm and 8.6% of those in the crizotinib arm were still receiving the study treatment.

No new safety signals were reported. Grade ≥3 adverse events (AEs) occurred in 52.0% and 56.3% of patients in the alectinib and crizotinib arms, respectively. In the alectinib arm, the most common grade ≥3 AEs were anemia (5.9%), increased aspartate transaminase (AST; 5.3%), increased alanine aminotransferase (4.6%), and pneumonia (4.6%). In the crizotinib arm, the most common grade ≥3 AEs were increased alanine aminotransferase (15.9%), increased AST (10.6%), neutropenia (5.3%), and increased blood creatine phosphokinase (4.0%). Similar percentages of patients in the alectinib and crizotinib arms reported AEs leading to dose reductions (20.4% and 19.9%, respectively) and treatment discontinuations (14.5% and 14.6%, respectively).

The researchers stated that ALEX is the first global randomized study to demonstrate improvement of both PFS and OS using a next-generation ALK TKI compared with crizotinib in patients with treatment-naïve ALK-positive NSCLC.

Mok T, et al. Ann Oncol. 2020;31:1056-1064.

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Last modified: February 8, 2021

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