# Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer

Source: https://onco.cc/key-papers/paper-peters-alex-alectinib-crizotinib-nejm-2017/  
OnCo record `paper-peters-alex-alectinib-crizotinib-nejm-2017` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A newer ALK drug that gets into the brain beat the original one, and did it with fewer side effects. ALEX is why nobody starts an ALK-positive patient on crizotinib any more.

## Summary

The ALEX trial investigators, reported by Peters, Camidge, Shaw and colleagues, randomised 303 patients with previously untreated advanced ALK-positive non-small-cell lung cancer, including those with asymptomatic central nervous system disease, to alectinib 600 mg twice daily or crizotinib 250 mg twice daily. The primary endpoint was investigator-assessed progression-free survival; time to central nervous system progression was a secondary endpoint.

The design deliberately admitted patients with brain metastases rather than excluding them, which is why the trial could show what the next generation of ALK inhibitors was actually for. It is the pattern later followed by CROWN with lorlatinib.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Tags: lung-evidence
- Journal: New England Journal of Medicine
- Year: 2017
- DOI: 10.1056/NEJMoa1704795
- Authors: Peters S, Camidge DR, Shaw AT, et al.
- Findings: Twelve-month event-free survival 68.4 percent (95 percent confidence interval 61.0 to 75.9) with alectinib against 48.7 percent (40.4 to 56.9) with crizotinib.; Hazard ratio for disease progression or death 0.47 (0.34 to 0.65).; Progression or death occurred in 62 of 152 patients (41 percent) on alectinib and 102 of 151 (68 percent) on crizotinib, at a median follow-up of 18.6 and 17.6 months.; Alectinib showed superior efficacy and lower toxicity than crizotinib in primary treatment of ALK-positive disease.
- What it means: First-line ALK treatment moved to a drug designed for the brain, and brain metastasis prevention became an explicit design goal rather than a hoped-for side effect. ALK-positive lung cancer is now among the longest-surviving metastatic solid tumours.
- Caveats: Open-label design with investigator-assessed primary endpoint, though an independent review committee endpoint agreed.; Asymptomatic central nervous system disease was allowed but symptomatic disease was not, so the hardest patients were not tested.; Superseded in first line by lorlatinib on progression-free survival grounds (CROWN), without a head-to-head overall survival comparison.

## Sources

- N Engl J Med 2017: https://doi.org/10.1056/NEJMoa1704795
- PubMed: https://pubmed.ncbi.nlm.nih.gov/28586279/
- ClinicalTrials.gov NCT02075840: https://clinicaltrials.gov/study/NCT02075840

## Connected records

- key papers: [Alectinib in resected ALK-positive non-small-cell lung cancer](https://onco.cc/key-papers/paper-wu-alina-adjuvant-alectinib-nejm-2024/), [Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer](https://onco.cc/key-papers/paper-kwak-crizotinib-alk-nsclc-nejm-2010/), [First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer](https://onco.cc/key-papers/paper-shaw-crown-lorlatinib-crizotinib-nejm-2020/)
- cancers: [ALK-positive non-small-cell lung cancer](https://onco.cc/cancers/alk-positive-nsclc/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- fronts: [Targeted Therapy](https://onco.cc/fronts/targeted-therapy/)
- technologies: [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [ALK](https://onco.cc/targets/alk/)
- drugs: [Alectinib](https://onco.cc/drugs/alectinib/), [Crizotinib](https://onco.cc/drugs/crizotinib/)
- companies: [Roche / Genentech](https://onco.cc/companies/roche-genentech/)
- terms: [Brain metastases (intracranial disease)](https://onco.cc/terms/brain-metastases/), [Driver mutation](https://onco.cc/terms/driver-mutation/)
- trials: [ALEX](https://onco.cc/trials/alex/)
- people: [Alice T. Shaw](https://onco.cc/people/alice-shaw/), [Solange Peters](https://onco.cc/people/solange-peters/), [Tony S. K. Mok](https://onco.cc/people/tony-mok/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/), [The brain: barrier and sanctuary](https://onco.cc/bottlenecks/b-brain-delivery/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- roadmaps: [Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch](https://onco.cc/roadmaps/lung-cancer-evidence-roadmap/)
- ideas: [Measure brain metastasis prevention as a primary endpoint, not as a secondary one](https://onco.cc/ideas/idea-lung-brain-metastasis-prevention-as-a-primary-endpoint/)

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