A 68-Year-Old Woman with ALK+ Non–Small Cell Lung Cancer - Episode 1

Case Overview: 68-Year-Old Woman with ALK+ NSCLC

Karen Reckamp, MD, provides an overview of the case of a 68-year-old woman with ALK+ NSCLC, including the initial presentation, clinical work-up, treatment, and the importance of molecular testing.

Karen Reckamp, MD: Hello, I’m Karen Reckamp. I’m the division director for medical oncology at Cedars-Sinai, and we’ll be talking about ALK-positivenon–small cell lung cancer today, starting with a case. This is a 68-year-old woman who presented with fatigue, decreased appetite, and some shortness of breath. The past medical history was unremarkable, and on a physical examination, wheezing was heard on auscultation in the lower lobes. Her ECOG performance status was 1. For her clinical work-up, laboratory test results were within normal limits, and a chest x-ray showed a left lower lobe mass. Subsequently, a CT scan of the chest, abdomen, and pelvis showed a 6.8-cm mass in the left lower lobe and a lesion within the liver that was suspicious for metastatic disease. A PET [positron emission tomography]/CT showed activity in the left lower lobe and in the liver. An MRI of the brain showed several subcentimeter lesions without edema. She underwent a bronchoscopy with transbronchial biopsy of the left lower lobe mass, and this confirmed lung adenocarcinoma, TTF-1 [thyroid transcription factor 1]-positive, and napsin A-positive. The tissue was sent for comprehensive molecular testing. First PD-L1 came back, and the tumor proportion score was 0%. Next-generation sequencing revealed EML4/ALK fusion; EGFR, ROS1, BRAF, KRAS, NTRK, MET, and RET were all negative for alteration. At this time, she was started on brigatinib at 90 mg daily for the first 7 days. This was well tolerated, and the dose was escalated to 180 mg daily.

Initially being diagnosed with metastatic non–small cell lung cancer with a lung mass and metastatic disease to the liver, her prognosis has changed over the years. Now that we have more targeted therapies for patients, and we have immunotherapy for patients, this has extended the lifespan. We have some data in The New England Journal of Medicine that showed that even patients with metastatic disease are living longer now than they were a decade ago, and this is largely because of targeted therapy. The fact that she had molecular testing is important. Generally, we do get PD-L1 testing to evaluate for the use of immune checkpoint inhibitor therapy as monotherapy. In this case, this was low, but even if this is a high level, we want to make sure that patients’ comprehensive molecular testing returns before we start frontline therapy.

We do comprehensive molecular testing on all patients with lung cancer and recommend that this should be a comprehensive test, next-generation sequencing. The optimal way to test is both DNA and RNA, which can increase the detection of fusions and rare mutations. This should be done at the time of diagnosis so that we don’t delay frontline therapy. With this patient, this was done and the tissue was sufficient. If there’s not sufficient tissue, we do perform a liquid biopsy, which can be beneficial in the frontline setting when there’s a significant tumor burden. If that liquid biopsy demonstrates a genetic alteration, this is something we’ve learned we can treat based on [the alteration].

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

Treatment

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