- Lorlatinib led to longer PFS and intracranial (IC) response rates compared with crizotinib in first-line treatment of patients with ALK-positive NSCLC.
- The safety profile of lorlatinib was consistent with that previously reported.
- Results support lorlatinib as a new first-line option in these patients.
Why this matters
- Resistance to anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) commonly develops and often includes central nervous system progression.
- Phase 3, open-label study.
- 296 patients (23 countries) randomly assigned to oral lorlatinib (100 mg once daily) or crizotinib (250 mg twice daily).
- Primary endpoint: PFS by blinded independent central review (BICR).
- Secondary endpoints: PFS by investigator (INV), objective response (OR) and IC-OR by BICR, duration of response (DOR), IC-DOR, OS, safety.
- Funding: Pfizer Inc.
- At data cutoff, median follow-up for PFS by BICR at data cutoff:
- 18.3 months for lorlatinib (n=149) vs 14.8 months for crizotinib (n=147).
- PFS by BICR was significantly prolonged by 72% with lorlatinib:
- HR, 0.28 (stratified 1-sided P<.001>
- 12-month PFS rate by BICR: 78.1% with lorlatinib vs 38.7% with crizotinib.
- PFS by INV: HR, 0.21 (stratified 1-sided P<.001>
- Complete/partial response: 76% with lorlatinib vs 58% with crizotinib.
- IC-OR by BICR: 83% with lorlatinib and 23% with crizotinib in patients with measurable brain metastases at baseline.
- Most adverse events in the lorlatinib group were related to laboratory abnormalities (mainly lipid profile).
“This is a very remarkable study. We now have multiple options for first-line ALK TKI therapy, but we’re still not curing patients. We need to make sure that all patients have molecular testing for ALK and all the actionable biomarkers,” said Christine M. Lovly, associate professor of medicine, co-leader Translational Research and Interventional Oncology Research Program, Vanderbilt University Medical Center, Vanderbilt Ingram Cancer Center, Nashville, TN, USA, who was not affiliated with the study.
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