Design: Phase 3 randomised trial (E4512)
Population: 153 patients with resected, centrally confirmed ALK-positive NSCLC
Primary outcome: Disease-free survival
Effect: Median 74.6 vs 75.1 months; HR 1.08 (95% CI 0.61 to 1.90)

E4512, published in August 2026, randomised 166 patients with resected stage IB to III ALK-positive non-small-cell lung cancer to two years of crizotinib or observation. Accrual stopped when adjuvant alectinib was approved in the US.

In 153 centrally confirmed patients, median disease-free survival was 74.6 months with crizotinib and 75.1 months with observation (hazard ratio 1.08, 95% CI 0.61 to 1.90). Grade 3 or higher adverse events occurred in 58% of crizotinib patients.

The result confirms that the first-generation agent does not carry the adjuvant benefit seen with alectinib. Where crizotinib is cheaper or more accessible, including in India, it should not be used as a substitute in the adjuvant setting on this evidence.

Test resected non-squamous lung cancer for ALK when adjuvant therapy is being considered.
Do not use crizotinib as an adjuvant substitute for alectinib.
Discuss the toxicity of two years of adjuvant targeted therapy.
Reserve crizotinib for settings where it has shown benefit.

Why it matters

Cheaper targeted drugs are sometimes used off-label in the adjuvant setting where they have not been shown to work.

The statistics, in plain English

A hazard ratio of 1.08 with an interval from 0.61 to 1.90 means no detectable benefit, and the trial was small. Median disease-free survival over six years in both arms reflects how well these patients do after surgery.