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ALEX showed that alectinib, a second-generation ALK drug that gets into the brain, kept ALK-positive lung cancer under control for about three years against less than one with crizotinib, and cut brain progression by three quarters.
ALEX randomised 303 patients with untreated advanced ALK-positive non-small-cell lung cancer to alectinib or crizotinib. Crizotinib had been the first ALK inhibitor, approved in 2011, but most patients progressed within a year, often in the brain, where the drug penetrates poorly.
At 12 months the cumulative incidence of brain progression was 9.4 percent with alectinib against 41.4 percent with crizotinib. In the updated analysis median investigator-assessed progression-free survival was 34.8 months against 10.9 months (hazard ratio 0.43), and five-year overall survival was 62.5 percent against 45.5 percent.
The FDA approved alectinib for first-line use in November 2017; the trial moved a second-generation inhibitor to the front and set the template that CROWN followed with lorlatinib.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
303 enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Progression-free survival (investigator, updated)primary | Alectinib | 152 | 34.8 months | 0.43 | - | link |
| Crizotinib | 151 | 10.9 months | ||||
| Overall survival at 5 years | Alectinib | 152 | 62.5% | - | - | link |
| Crizotinib | 151 | 45.5% |
A second publication from the ALEX trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.
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.
Shares D. Ross Camidge, eXalt3, ASCEND-4, PROFILE 1014.
Shares D. Ross Camidge, eXalt3, ASCEND-4, PROFILE 1014.
Shares Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer, Alectinib, Brain metastases (intracranial disease), ALK-positive non-small-cell lung cancer.
Shares D. Ross Camidge, Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer, Crizotinib, Brain metastases (intracranial disease).
Shares D. Ross Camidge, Brain metastases (intracranial disease), ALK-positive non-small-cell lung cancer, ALK.
Shares Alectinib, ALK-positive non-small-cell lung cancer, ALK, Roche / Genentech.
Shares Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer, Crizotinib, Brain metastases (intracranial disease), ALK-positive non-small-cell lung cancer.
Shares J-ALEX, Alectinib, Roche / Genentech, Non-small-cell lung cancer.