First-line Treatment Options for ALK+ mNSCLC


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

Initial presentation

  • A 57-year-old man presented with fatigue, anorexia, and occasional rib pain
  • PMH: unremarkable
  • PE: mild right-sided chest tenderness on palpation 

Clinical workup

  • Labs: WNL 
  • Chest x-ray showed multiple right upper lobe masses
  • Chest/abdomen/pelvic CT scan confirmed 3 masses (largest 6.5 cm)
  • PET scan showed activity in the right upper lobe masses
  • MRI of the brain showed multiple scattered lesions, consistent with multifocal brain
  • Bronchoscopy with transbronchial biopsy of the right upper lobe mass confirmed lung adenocarcinoma, invasive mediastinal
  • Stage IV adenocarcinoma; ECOG PS 0
  • Molecular testing: ALK fusion+, EGFR-, ROS1-, BRAF-, KRAS-, NTRK-, MET-, RET-, PD-L1 0% by IHC


  • Patient was started on brigatinib 90 mg qDay for 7 days; well tolerated; dose was increased to 180 mg qDay

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