MedNet.nl: A new post-hoc analysis of the phase 3 CROWN study shows that dose reduction of lorlatinib has a positive effect on the occurrence of side effects and that this allowed patients to continue to benefit from the treatment for a long time.
The registration of lorlatinib as first-line treatment for ALK-positive non-small-cell lung cancer is based on the results of the CROWN study. This study showed that lorlatinib led to longer progression-free survival (PFS) and higher intracranial response rates. Last year at ASCO, the 5-year update of the study was presented, which showed that the median PFS in the lorlatinib arm after a median follow-up of 60.2 months had not yet been reached, while it was 9.1 months in the crizotinib arm. At the 2025 ASCO Annual Meeting, researchers presented an analysis looking at the effect of dose modifications.
In the lorlatinib group (n=149), 49 patients (33%) had at least 1 dose reduction. Twenty-four patients had one dose reduction (to 75 mg QD) and 25 patients underwent two dose reductions (to 50 mg QD). Furthermore, 45 patients had at least one treatment interruption. The median duration of interruption was 1.2 months.
The dose reductions had a positive effect on the severity of side effects. In patients with one dose reduction, the side effect cleared up completely in half of the cases. In 25% this was partially the case and in patients with two dose reductions these percentages were 71% and 8%.
The dose reductions allowed patients to continue to be treated with lorlatinib for a long time. With a dose reduction to 75 mg, patients were treated for a median of 42.2 months, and with a second dose reduction to 50 mg, they were treated for a median of 20.7 months.
These results highlight the importance of dose reductions of lorlatinib and allow treatment to be continued for longer periods of time, the researchers said.
This article was originally published in Dutch on MedNet.nl