ALK+ mNSCLC: Advancements Made and What’s Next


An expert in the treatment of lung cancer gives insight for the sequencing of ALK inhibitors following disease progression, highlighting the instances of the development of brain involvement and rebiopsy.

Karen Reckamp, MD: The progress we’ve made to date in treating ALK-positive metastatic non–small cell lung cancer is astounding. We have a large number of frontline therapies that are incredibly beneficial to patients’ tumor responses and significantly prolong progression-free survival. By sequencing these, we have some of the best overall survival that we’ve ever seen with metastatic non–small cell lung cancer. Moving to the future, we need to keep working on these mechanisms of resistance because we’re still not curing most patients. We need to better understand how to utilize immune checkpoint inhibitors for patients with ALK fusion-positive non–small cell lung cancer.

In small studies, it appears that patients with ALK fusions have less efficacy with immune checkpoint inhibitor therapy, at least as monotherapy. We don’t know how well they do with chemotherapy, or if chemotherapy is sufficient on its own. We need to understand how to make tumors that are generally cold, such as many of the ALK+ tumors, into hot tumors that will respond to immunotherapy, which may lead us toward more cures with this disease. Then we need to think about screening. At this point, many of these patients are light- or never-smokers, they’re not included in our screening algorithms. We are looking for prognostic markers to define who might benefit from early screening. From the early study presented from Taiwan, patients who are nonsmokers who have a family history of lung cancer may benefit from early CT screening. This will also be something that will help improve cures for our patients.

Transcript edited for clarity.

Case: A 68-Year-Old Woman with ALK+ Non–Small Cell Lung Cancer

Initial presentation

  • A 68-year-old woman presented with fatigue, wheezing and decreased appetite
  • PMH: unremarkable
  • PE: wheezing on auscultation; ECOS PS 1

Clinical Workup

  • Labs: WNL 
  • Chest x-ray showed a left lower lobe mass
  • Chest/abdomen/pelvic CT scan confirmed a 6.8-cm left lower lobe lung mass and a suspicious liver lesion
  • PET scan showed activity in the left lower lobe mass and liver
  • MRI of the brain showed several subcentimeter lesions without edema
  • Bronchoscopy with transbronchial biopsy of the left lower lobe mass confirmed lung adenocarcinoma
  • Molecular testing: NGS revealed EML4/ALK fusion+, EGFR-, ROS1-, BRAF-, KRAS-, NTRK-, MET-, RET-, PD-L1 0% by IHC
  • Staging: IVB adenocarcinoma


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

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