NSCLC: ALK mutations could signal better lorlatinib results

  • Shaw AT & al.
  • J Clin Oncol
  • 20 Mar 2019

  • curated by Kelli Whitlock Burton
  • Univadis Clinical Summaries
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Takeaway

  • 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.

Study design

  • 198 patients with ALK-positive NSCLC received 100 mg daily lorlatinib in a phase 2 trial.
  • Funding: Pfizer and National Cancer Institute.

Key results

  • 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).

Limitations

  • Only 51% of tumor specimens were de novo; archival specimens may have been collected at different disease stages.