- 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.
- 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.
- 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.
- Small study size.