First-Line Treatment Options in ALK+ Lung Cancer

Lyudmila Bazhenova, MD: For patients with newly diagnosed ALK-positive stage IV non–small cell lung cancer, several ALK tyrosine kinase inhibitors have approval in the first line: crizotinib, ceritinib, alectinib, and brigatinib. We have 2 randomized trials comparing alectinib versus crizotinib and brigatinib versus crizotinib. Both of those trials showed that later-generation tyrosine kinase inhibitors, or second-generation tyrosine kinase inhibitors, as we call them, definitely have more efficacy compared with crizotinib. In my view, there are 2 front-runners for newly diagnosed ALK-mutant stage IV non–small cell lung cancer, and those are alectinib and brigatinib.

The patient has asymptomatic small brain metastases. We know that second-generation ALK tyrosine kinase inhibitors are highly CNS [central nervous system] penetrant and have established CNS activity. In the patient who has no symptoms and small brain metastases without significant edema, it would have been very reasonable to delay brain radiation, give that patient alectinib, repeat a brain MRI in about 6 weeks, and then use radiation as salvage therapy if the tumors did not respond to tyrosine kinase inhibitors.

In my opinion, it is important to make decisions in collaboration with your radiation oncologist. Sometimes you may have a tumor in the brain that is in a dangerous location, like close to the midbrain, where even small enlargement of the tumor can cause adverse effects. So as long as your radiation oncologist is comfortable with delaying radiation for 6 weeks to see if tyrosine kinase inhibitors will work, I think it is reasonable to do so.

Transcript edited for clarity.

Case: A 58-Year-Old Woman With ALK+ NSCLC

Initial presentation

  • A 58-year-old woman presented with cough, fatigue and anorexia
  • PMH: unremarkable
  • PE: unremarkable

Clinical Workup

  • Labs: WNL
  • Imaging:
    • Chest x-ray showed multiple left upper lobe mass and mediastinal lymphadenopathy
    • Chest/abdomen/pelvic CT scan confirmed left upper lobe mass measuring 6.2 cm
    • PET scan showed PET positivity in bilateral LUL mass and mediastinal LN
    • MRI of the brain showed widespread scattered small lesions; consistent with multifocal brain metastases
  • Bronchoscopy with transbronchial biopsy of the left upper lobe confirmed lung adenocarcinoma
  • Molecular testing: ALK fusion+, EGFR-, ROS1-, BRAF-, KRAS-, NTRK-, MET-, RET-
  • Staging: IVA adenocarcinoma; ECOG PS 1


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

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