ROS1 NSCLC: positive results from phase 1-2 lorlatinib trial

  • Lancet Oncol

  • curated by Kelli Whitlock Burton
  • Univadis Clinical Summaries
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Takeaway

  • Lorlatinib demonstrated promising response rates and PFS in patients with ROS1-positive NSCLC, with an acceptable safety profile.

Why this matters

  • Crizotinib is the only tyrosine kinase inhibitor (TKI) approved for patients with ROS1-positive NSCLC, but treatment resistance is common.

Study design

  • Open-label, single-group, international, phase 1-2 trial.
  • 69 patients with ROS1-positive NSCLC received lorlatinib.
  • Median follow-up, 21.1 months.
  • Funding: Pfizer.

Key results

  • 30% were TKI-naive, 58% had received crizotinib as their only TKI, and 12% had received 1 noncrizotinib ROS1 TKI or ≥2 ROS1 TKIs.
  • 57% had central nervous system metastases at baseline.
  • Objective response was reported in 41% of the entire patient cohort, 62% of TKI-naive patients, 35% of crizotinib-treated patients, and 45% of patients with CNS metastases at baseline.
  • 64% of TKI-naive patients and 50% of crizotinib-treated patients had an intracranial response.
  • Median duration of response was 25.3 months in TKI-naive patients and 13.8 months in crizotinib-treated patients.
  • PFS was 21.0 months in TKI-naive patients and 8.5 months in crizotinib-treated patients.
  • 96% of patients had ≥1 adverse event (AE), and 7% had a serious AE.
  • Hypertriglyceridemia and hypercholesterolemia were the most common grade 3-4 AEs.

Limitations

  • Small study size.