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Lung: First-line ALK-positive NSCLC

Free question published 27 October 2026

RespiratoryFirst-line ALK-positive NSCLC

A 47-year-old never-smoker presents with metastatic lung adenocarcinoma involving the liver and multiple small asymptomatic brain metastases. Next-generation sequencing identifies an ALK rearrangement; there is no EGFR mutation. She has WHO performance status 1. Considering both systemic and intracranial disease control, which first-line systemic therapy is most appropriate?

  1. ACrizotinib
  2. BSingle-agent pembrolizumab
  3. COsimertinib
  4. DCisplatin-pemetrexed chemotherapy
  5. EAlectinib

Why E is correct

In the ALEX trial, the next-generation ALK inhibitor alectinib gave markedly superior progression-free survival versus crizotinib (median PFS 34.8 versus 10.9 months) and substantially reduced CNS progression (12% versus 45% of patients; cause-specific HR 0.16). Its high CNS activity makes it the preferred first-line choice in ALK-positive disease with brain metastases.

And why the others are not

  • ACrizotinib was the inferior comparator in ALEX, with far higher rates of CNS progression and shorter PFS.
  • BSingle-agent pembrolizumab is reserved for driver-negative disease; immunotherapy is not the first-line treatment for ALK-rearranged NSCLC.
  • COsimertinib targets EGFR mutations, not ALK rearrangements, and would be ineffective here.
  • DPlatinum chemotherapy alone is inferior to a targeted ALK inhibitor as first-line therapy in ALK-positive disease.

Source ALEX - Alectinib versus crizotinib in untreated ALK-positive NSCLC — Peters S, Camidge DR, Shaw AT, et al. Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2017;377(9):829-838.

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