Dr. Sabari on Selecting Between Available ALK inhibitors in ALK+ NSCLC

Joshua K. Sabari, MD, assistant professor, Department of Medicine, NYU Langone Health’s Perlmutter Cancer Center, discusses selecting between available ALK inhibitors in ALK-positive non–small cell lung cancer (NSCLC).

Selecting frontline treatment for patients with ALK-positive NSCLC can be difficult because several ALK inhibitors are approved for use, including crizotinib (Xalkori), alectinib (Alecensa), brigatinib (Alunbrig), and lorlatinib (Lorbrena), Sabari explains. In clinical practice, Sabari prefers to utilize alectinib at 600 mg twice daily in the frontline setting based on the efficacy data observed with the agent in the phase 3 ALEX (NCT02075840) and J-ALEX (JapicCTI-132316) trials.

Alectinib has demonstrated significantly improved progression-free survival vs crizotinib in patients with ALK-positive NSCLC. Moreover, the agent is well tolerated, elicits good central nervous system (CNS) activity, and has some activity against resistance mechanisms elicited by early-generation ALK inhibitors, Sabari says.

Data from the phase 3 CROWN trial (NCT03052608) showed that lorlatinib was superior in terms of efficacy vs crizotinib. Although lorlatinib could have better CNS activity vs alectinib, lorlatinib is associated with neurologic toxicities, such as neurocognitive complications, ataxia, and dizziness. Because of this, Sabari reserves lorlatinib for use in the second-line setting for patients with ALK-positive NSCLC. Additionally, following alectinib and lorlatinib, patients should be considered for clinical trial enrollment, Sabari concludes.