Dr. Liu on ALK-Targeted Agents in NSCLC

Stephen Liu, MD, associate professor of medicine, Division of Hematology and Oncology, Georgetown University Medical Center, discusses ALK-targeted agents in the field of non—small cell lung cancer (NSCLC).

Brigatinib (Alunbrig) is the most recent ALK-targeted agent to be FDA approved. It was approved in the second-line setting, post-crizotinib (Xalkori). It maintains in vitro activity in the presence of other resistance mutations, as is the case in the salvage setting. However, this has yet to be validated in the clinic, says Liu.

Ensartinib and lorlatinib maintain activity in the presence of solvent-front mutations, states Liu. They have very high central nervous system penetration and a favorable toxicity profile. Ensartinib has shown response rates of about 80% in tyrosine kinase inhibitor- (TKI) naïve patients. Post-crizotinib, response rates are approximately 72%. Following at least 2 prior TKIs, ensartinib has been shown to maintain activity with response rates approaching 25%.

Lorlatinib has shown response rates of over 40% with at least 2 prior TKIs, fostering its use in the salvage setting. Physicians do not yet know what its efficacy translates to in the frontline setting. Alectinib (Alecensa) has shown progression-free survival of over 2 years, but starting with lorlatinib, and ensartinib may widen the range of possibilities, says Liu.