ALTA
ALTA tested two doses of brigatinib in ALK-positive lung cancer that had progressed on crizotinib; the higher dose, started after a lower-dose first week, gave more responses and longer control, including in the brain.
Overview
ALTA (ALK in Lung Cancer Trial of AP26113) was a randomised phase 2 trial of brigatinib in ALK-positive non-small-cell lung cancer that had progressed on crizotinib. It randomised 222 patients 1:1 to brigatinib 90 mg once daily (arm A, 112 patients, 109 treated) or 180 mg once daily after a 7-day lead-in at 90 mg (arm B, 110 patients), stratified by brain metastases and best response to crizotinib. At baseline 69 percent had brain metastases and 74 percent had received chemotherapy. The primary endpoint was investigator-assessed confirmed objective response rate; there was no arm without brigatinib.
At a median follow-up of 8.0 months the confirmed response rate was 45 percent in arm A and 54 percent in arm B, and median progression-free survival was 9.2 and 12.9 months. Among patients with measurable brain metastases, independent review found intracranial responses in 11 of 26 (42 percent) and 12 of 18 (67 percent). Common adverse events were nausea, diarrhoea, headache and cough, mostly grade 1 or 2. A subset of pulmonary adverse events with early onset (median day 2) occurred in 14 of 219 treated patients (grade 3 or higher in 3 percent) and none occurred after escalation to 180 mg in arm B (Journal of Clinical Oncology 2017).
The authors concluded that 180 mg with the lead-in was consistently more effective than 90 mg with acceptable safety. The trial supported the 2017 US approval of brigatinib after crizotinib; ALTA-1L then tested it against crizotinib in untreated disease.
- 45 vs 54 out of 100 had their tumour shrink with Brigatinib 90 mg compared with Brigatinib 180 mg (7-day 90 mg lead-in); 9 fewer per 100.
- On this measure the first group did worse, not better.
- A response rate counts how many people had their tumours shrink by a set amount; shrinking is encouraging but does not by itself show that people live longer or feel better.
- Median 9.2 vs 12.9 months with Brigatinib 90 mg compared with Brigatinib 180 mg (7-day 90 mg lead-in); about 3.7 months shorter 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.
- 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.
- 42 vs 67 out of 100 had their tumour shrink with Brigatinib 90 mg compared with Brigatinib 180 mg (7-day 90 mg lead-in); 25 fewer per 100.
- On this measure the first group did worse, not better.
- A response rate counts how many people had their tumours shrink by a set amount; shrinking is encouraging but does not by itself show that people live longer or feel better.
- These results apply to the people the trial enrolled: ALK-positive advanced non-small-cell lung cancer that progressed on crizotinib: two brigatinib dose regimens, randomised, no control arm. 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.
222 enrolled.
97.5% CI 34 to 56; 112 randomised, 109 treated · 97.5% CI 43 to 65
Source11 of 26 · 12 of 18
Source| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Confirmed objective response rate (investigator)primary | Brigatinib 90 mg | 112 | 45% | - | - | link |
| Brigatinib 180 mg (7-day 90 mg lead-in) | 110 | 54% | ||||
| Progression-free survival (investigator) | Brigatinib 90 mg | 112 | 9.2 months | - | - | link |
| Brigatinib 180 mg (7-day 90 mg lead-in) | 110 | 12.9 months | ||||
| Intracranial objective response rate (independent review, measurable brain metastases) | Brigatinib 90 mg | 26 | 42% | - | - | link |
| Brigatinib 180 mg (7-day 90 mg lead-in) | 18 | 67% |
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not linked directly; found by shared links- Key paperCROWN: lorlatinib versus crizotinib as first treatment for ALK-positive lung cancer
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