Approaching TKI (tyrosine kinase inhibitor)-based therapy for the first-line management of ALK+ mNSCLC.
Joshua M. Bauml, MD: There are multiple tyrosine kinase inhibitors approved for first-line management of ALK-positive non–small cell lung cancer. When I look at them, there are 2 classes; the older drugs, crizotinib and ceritinib, which don’t have a lot of CNS [central nervous system] penetration, and the newer drugs approved in the first line, notably alectinib and brigatinib. Alectinib and brigatinib are both highly CNS penetrant ALK inhibitors, which are highly effective in the treatment of ALK+ non–small cell lung cancer. In the ALTA-1L study, brigatinib was found to be superior to crizotinib in terms of progression-free survival. In the ALEX study, the same finding was found for alectinib as compared to crizotinib.
How do I decide which one to use? Honestly, I think either are completely reasonable; it ends up being a bit of a coin flip in terms of which treatment we would use. The toxicity profile is a little different between these agents. Alectinib seems to have a higher rate of liver function test elevations, whereas brigatinib has a rare pulmonary event that happens usually early in the treatment. In terms of how we incorporate brain metastases into that treatment decision algorithm, both alectinib and brigatinib are highly CNS penetrant. If I have a patient who has brain metastases and if they’re asymptomatic and relatively small, I will often start with a tyrosine kinase inhibitor and follow closely with my colleagues in radiation oncology to ensure that the patient is having a nice response in the brain. I follow these patients very closely; I tend to see them in my medical oncology clinic about every 6 weeks, once with the nurse practitioner I work with, and then alternating with a scan and a visit with me. Then when we compare that to the radiation oncology follow-up for brain metastases, it’s dependent on how the brain metastases are working; I work closely with my colleagues in radiation oncology for that scheduling.
This transcript was edited for clarity.
A 57-Year-Old Man with ALK+ NSCLC