Mitigating CNS Events Is “Key” With Lorlatinib for ALK-Positive NSCLC

CancerNetwork® spoke with Misako Nagasaka, MD, PhD, about important considerations for managing central nervous system (CNS) toxicity in patients who receive lorlatinib (Lorbrena) for ALK-positive non–small cell lung cancer (NSCLC). She highlighted these strategies in the context of 5-year progression-free survival data from the phase 3 CROWN trial (NCT03052608) presented at the 2024 American Society of Clinical Oncology Annual Meeting.

Although CNS adverse effects were not unexpected toxicities, Nagasaka, an associate clinical professor of medicine in the Division of Hematology and Oncology at the University of California, Irvine (UCI) School of Medicine of UCI Health, stated that most of these events were grade 1 or 2 in the CROWN trial. With these data in mind, she described how only a portion of patients may require treatment interruptions or reductions to mitigate CNS toxicities. She concluded that it is crucial to counsel patients and their family members on the likelihood of CNS toxicities during treatment with lorlatinib.

Transcript:

As far as the toxicities go, many of us are not so much concerned with hyperlipidemia but much more concerned with the potential CNS toxicities when using lorlatinib. However, that was not an unexpected toxicity. We have seen some CNS toxicity events from earlier studies using lorlatinib. It’s important to note that most of the CNS adverse events were grade 1 or 2, and the majority of patients, 58%, did not require any medical intervention or any intervention at all. They were able to continue the drug at the same dose, and the CNS [adverse] effects subsided on their own. It is only a portion of the patients who receive lorlatinib who have a CNS toxicity that needs to be managed with either a drug hold or drug reduction. But they are still there, and it’s important to make sure we don’t miss these patients. Counseling patients and family members on the possibility of these CNS toxicities remains key.

Reference

Solomon BJ, Liu G, Felip E, et al. Lorlatinib vs crizotinib in treatment-naïve patients with advanced ALK+ non-small cell lung cancer: five-year progression-free survival and safety from the CROWN study. J Clin Oncol. 2024;42(suppl 17):LBA8503.