Molecular Testing in ALK+ Non–Small Cell Lung Cancer


Lyudmila Bazhenova, MD: Molecular testing has to be part of the management for a patient with stage IV non–small cell lung cancer. Current guidelines recommend molecular testing for patients with nonsquamous non–small cell lung cancer and select patients with squamous cell lung cancer. Comprehensive molecular sequencing is encouraged, preferably with a next-generation sequencing panel. We have to test all patients regardless of gender, ethnicity, and smoking status.

Currently in lung cancer there are 7 molecular abnormalities with FDA-approved targeted therapies, and those are EGFR, ALK, ROS, BRAF V600E, NTRK, RET, and MET exon 14 skipping mutations. In addition, there are 3 other abnormalities—KRAS G12C, EGFR, and exon 20 insertions—as well as HER2 [human epidermal growth factor receptor 2] exon 20 insertions, for which there are compounds in clinical trials with preliminary evidence of efficacy. Therefore, it is important to make sure you are testing your patients for those mutations.

Currently, I believe that next-generation sequencing [NGS] is preferred because it does have ability to save tissue. You need less tissue to do NGS testing compared with if you do single-gene sequencing. Also, take into account the fact that we now need to test for at least 7, maybe even 10, molecular abnormalities. It is very possible that next-generation sequencing will also be cost saving.

My personal approach is to actually use both liquid and tissue next-generation sequencing at the time of the diagnosis, because I believe those tests are complementary. An alternative approach would be to do next-generation sequencing of tissue and save plasma next-generation sequencing, or what we also call the liquid biopsy, for patients whose tissue is insufficient. It’s very important to note that we need to wait until the molecular testing is back before we initiate therapy.

If you look at the turnaround times, the turnaround time for PD-L1 testing is actually about 2 to 3 days. The turnaround time for a liquid biopsy is about 10 days or so, and it is about 2 to 3 weeks for tissue next-generation sequencing results. So you will have the PD-L1 test results come in before you have molecular testing results, and unless your patient is rapidly declining, it is very important to wait for the molecular testing results before you start therapy. If you have to start therapy right away and don’t feel like you can wait for the molecular testing results, I recommend you just give chemotherapy. We do have emerging evidence that suggests that tyrosine kinase inhibitors may cause immune-related adverse events, such as pneumonitis and in some cases hepatitis, when given after immunotherapy.

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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