ALTA-1L , briga vs crizo

Background

Phase III, open-label RCT (ALTA-1L). N=275. Advanced, treatment-naïve ALK-positive NSCLC. First-line brigatinib vs crizotinib.

Interventions and follow up

Arm A: Brigatinib 180 mg PO daily with 7-day lead-in at 90 mg
Arm B: Crizotinib 250 mg PO BID
Primary endpoint: PFS by blinded independent review. Secondary: ORR, intracranial response
mFollow up: 24.9 mo

Results

mPFS: 24 mo vs 11 mo, HR 0.49 (95% CI 0.35–0.68; log-rank P<.0001)
12-mo PFS: 67% vs 43%, HR 0.49 (95% CI 0.33–0.74; P<.001)
ORR: 71% vs 60%
Intracranial response rate: 78% vs 29%
12-mo OS: 85% vs 86%; mOS not reached in either arm
2-yr OS: 76% vs 74%

Adverse events

Brigatinib, grade 3–4: Elevated CK 39% vs 15%, cough 25% vs 16%, hypertension 23% vs 7%, elevated lipase 19% vs 12%
Crizotinib, more frequent: GI toxicity (diarrhea, nausea, vomiting), peripheral edema, photopsia, dysgeusia, visual impairment

Conclusions

Brigatinib significantly improved PFS, ORR, and intracranial response over crizotinib in treatment-naïve ALK-positive NSCLC, supporting brigatinib as a first-line option.

Key Limitations

Open-label design. Crizotinib comparator now superseded as preferred 1L. No head-to-head vs alectinib or lorlatinib. OS immature at this analysis. Brigatinib lead-in dosing needed to mitigate early-onset pulmonary events (not captured as standard grade categories).

Clinical Context

FDA approved brigatinib 1L ALK+ NSCLC (2020). ESMO lists brigatinib among preferred 1L ALK TKIs alongside alectinib and lorlatinib. Often selected for its once-daily dosing and intracranial activity; lorlatinib (CROWN) now favored in many fit patients.

References