First-line lorlatinib provides unprecedented improvement in outcomes for patients with ALK-positive non-small cell lung cancer

The phase 3 CROWN trial has demonstrated that first-line treatment with lorlatinib provides an “unprecedented” improvement in outcomes for patients with ALK-positive, advanced non-small cell lung cancer (NSCLC).

According to a presentation at the ASCO Annual Meeting 2024 by study presenter, Benjamin Solomon, MBBS, PhD, of Peter MacCallum Cancer Center in Melbourne, Australia, the median progression-free survival (PFS) was not reached after a follow-up of about 5 years with lorlatinib, and was 9.1 months with crizotinib.

Longest PFS reported in ALK-positive lung cancer with lorlatinib

The median PFS with lorlatinib corresponds to the longest PFS reported in ALK-positive lung cancer, and with any targeted therapy in advanced non-small cell lung cancer.

At a median follow-up of 60.2 months in the lorlatinib arm and 55.1 months in the crizotinib arm, the 24-month PFS rate was 70% with lorlatinib and 15% with crizotinib, the 36-month PFS rate was 65% and 10%, respectively, the 48-month PFS rate was 63% and 10%, respectively, and the 60-month PFS rate was 60% and 8%, respectively.

Lorlatinib demonstrates efficacy in patients with brain metastases

Among patients with brain metastases at baseline, the median PFS was not reached in the lorlatinib arm and was only 6 months in the crizotinib arm. The rate of intracranial progression was also lower in the lorlatinib arm compared to the crizotinib arm in both patients with and without brain metastases at baseline, with the median time to intracranial progression not reached in the lorlatinib arm and being 16.4 months in the crizotinib arm in the overall cohort.

Dr. Solomon noted that these results demonstrate the ability of lorlatinib not only to prevent the progression of existing brain metastases but also to prevent the development of new brain metastases.

Safety profile of lorlatinib

All patients in the lorlatinib arm experienced adverse events (AEs), with the rate of grade 3-4 AEs being 77% and the rate of serious AEs being 44%. The rate of central nervous system AEs was 42%.

While AEs led to dose reductions in 23% of patients in the lorlatinib arm and temporary treatment discontinuation in 62% of patients in this arm, the rate of permanent discontinuation was 11%, and 5% of discontinuations were due to treatment-related AEs. Notably, all treatment-related AEs leading to discontinuation occurred during the first 26 months of lorlatinib treatment.

Dose reductions in the first 16 weeks of treatment did not impact the efficacy of lorlatinib, with both the median PFS and time to intracranial progression not being reached in patients with dose reductions.

Conclusion

The systemic efficacy results, coupled with protection from intracranial progression and the absence of new safety signals, indicate that first-line lorlatinib provides an unprecedented improvement in outcomes for patients with ALK-positive non-small cell lung cancer.

This research was supported by Pfizer, and some study authors disclosed conflicts of interest.

The results of the CROWN trial were also published in the Journal of Clinical Oncology.

Originally Post From https://www.cancertherapyadvisor.com/reports/lorlatinib-longest-pfs-advanced-alk-nsclc/