- Patients with NSCLC who failed ≥1 second-generation anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) performed better with lorlatinib if they were positive for ALK mutations.
Why this matters
- Using ALK mutations as a biomarker could help clinicians identify which patients may benefit from lorlatinib.
- 198 patients with ALK-positive NSCLC received 100 mg daily lorlatinib in a phase 2 trial.
- Funding: Pfizer and National Cancer Institute.
- 24% of patients had ≥1 ALK mutations detected by plasma or tissue typing.
- Among crizotinib-resistant patients, efficacy of lorlatinib was similar regardless of ALK mutation status using both plasma and tissue testing.
- Among second-generation ALK-TKI-resistant patients, lorlatinib efficacy was better in patients with ALK mutations compared with those without mutations (objective response rate 62% vs 32% with plasma testing and 69% vs 27% with tissue testing).
- Median PFS was significantly better in patients with ALK mutations but only when using tissue typing (PFS, 11.0 vs 5.4 months; HR, 0.47; 95% CI, 0.27-0.83).
- Only 51% of tumor specimens were de novo; archival specimens may have been collected at different disease stages.