ALEX
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.
Overview
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.
- Median 34.8 vs 10.9 months with Alectinib compared with Crizotinib; about 23.9 months longer for half the group.
- A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
- Put another way, the treated group had about 57 percent lower chance of the event at any given time (hazard ratio 0.43).
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- 62.5 vs 45.5 out of 100 alive at 5 years with Alectinib compared with Crizotinib; 17 more per 100.
- Roughly one extra person helped for every 6 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
- Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
- These results apply to the people the trial enrolled: Untreated advanced ALK-positive non-small-cell lung cancer: alectinib versus crizotinib. People in a different situation may not see the same effect.
- The trial selected people by a biomarker (ALK); the result should not be assumed for people whose cancer does not have it.
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 participants 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% |
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