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57-Year-Old Never-Smoker with Dyspnea

Tom, a 57-year-old never-smoker, presented complaining of coughing, dyspnea, and fatigue. Other than mild hypertension controlled with losartan 100 mg, Tom has no comorbidities.

A chest X-ray reveals a mass in the left lung. Biopsy of the nodule was positive for non-small cell lung cancer and was an adenocarcinoma. A brain MRI was negative metastatic lesions. Molecular testing revealed that Tom had 0% expression of PD-L1 and was negative for EGFR, ROS1, and BRAF but was positive for ALK gene rearrangement.

Tom began treatment with crizotinib. After ten months of crizotinib therapy, Tom’s symptoms escalated — increased fatigue, back pain, and worsening dyspnea.

CT scans showed that his pulmonary nodules were increasing in size, had experienced nodal spread, and had developed lesions in several vertebrae. A brain MRI now shows disseminated small lesions.

What other tyrosine kinase inhibitor options might benefit Tom?
Could other treatment options, including targeted radiation, be helpful for this patient?

  • March 22, 2021
    I would attempt a repeat biopsy or at least run a liquid biopsy to see if a resistance mutation can be identified, for example, if we identified G1202R mutation, lorlatinib would be a great choice.
    Another option for rapidly progressive disease the IMPOWER-150 quadruple combo.
    In addition to a new systemic therapy (either TKI or chemo), I would add bone-directed therapy.
  • March 22, 2021
    pt with alk pos lung ca ,lorlatinib has marked brain penetration would consider lorlatinib ,though brigatinib and alcensa are other options
  • March 22, 2021
    I would recommend palliative radiation to the lesions causing his back pain. There are many options. I would recommend lorlatinib. Other options I have used include alectinib or brigatinib.