Alectinib vs. Crizotinib in Untreated ALK-Positive NSCLC

Title: Alectinib vs. Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer

Peters, S et al.


What You Need to Know:

In patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC), alectinib, a selective inhibitor of ALK, was found to be more efficacious and less toxic when compared to crizotinib.

Trial Design:

  • Open-label, phase 3 trial evaluated the efficacy of alectinib versus crizotinib in patients with previously untreated ALK-positive NSCLC
  • 303 patients were randomized to receive 600mg alectinib twice daily or 250mg crizotinib twice daily
  • Primary endpoint: investigator-assessed progression-free survival
  • Secondary endpoints: progression-free survival assessed by an independent review committee, time to central nervous system (CNS) progression, objective response rate, overall survival

Key Outcomes:

  • Median follow-up: 17.6 months for crizotinib patients, 18.6 months for alectinib patients
  • 41% of alectinib patients (62/152) experienced an event of disease progression or death vs 68% of crizotinib patients (102/151)
  • Significantly higher investigator-assessed progression-free survival rate for alectinib patients: 12-month event-free survival rate was 68.4% (95% CI: 61.0, 75.9) for alectinib patients vs 48.7% (95% CI: 40.4, 56.9) for crizotinib patients (HR for disease progression or death: 0.47; 95% CI: 0.34, 0.65; P<0.001)
  • Median progression-free survival was not reached with alectinib
  • “The results for independent review committee-assessed progression-free survival were consistent with those for the primary end point”
  • 12% of alectinib patients (18/152) experienced an event of CNS progression vs 45% of crizotinib patients (68/151) (cause-specific HR: 0.16; 95% CI: 0.10, 0.28; P<0.001)
  • 126 alectinib patients experienced a response (response rate: 82.9%; 95% CI: 76.0, 88.5) compared to 114 patients in the crizotinib group (response rate: 75.5%; 95% CI: 67.8, 82.1) (P=0.09)
  • 41% of alectinib patients experienced a grade 3 to 5 adverse event vs 50% of crizotinib patients