Case Presentation: ALK-Rearranged Metastatic NSCLC

Lyudmila A. Bazhenova, MD:We have a 50-year-old female who presented with right-sided chest pain, dyspnea, and coughing up blood. Her past medical history is significant for the fact that she is a nonsmoker and has no other medical conditions. Her workup included a CT scan of the chest, which showed a right-lung mass. A brain MRI showed a small brain metastasis, but the patient had no symptoms. A biopsy of the right lung showed adenocarcinoma. Molecular testing showed that she wasEGFRwild-type andKRASwild-type, and her immunohistochemical test was positive forALK.

A post progression biopsy was performed, and her mutational analysis showed anALKmutation, specifically I1171N. She was started on brigatinib at the FDA-approved 90-mg lead-in dose, which was later increased to 180 mg. She tolerated the treatment well and just had a little bit of a nausea. She developed a partial response to brigatinib, including a CNS [central nervous system] response, which is continuing at 15 months of therapy.

To summarize, we have a patient with stage 4 lung cancer andALKrearrangement. Her first line of treatment was crizotinib. Her second line of treatment was brigatinib. This presentation is very typical for patients withALKrearrangements. We have a nonsmoking patient. However, I’d like to stress 2 points. First, when she was diagnosed, she only had 3 molecular abnormalities tested, which wereEGFR,KRAS, andALK. In our current state, we have 4 molecular targeted agents approved for lung cancer. What’s missing from her molecular profile isROS1mutation as well asBRAFmutation testing.

The second point that I think is important to make is we do not make the decision of doing or not doing molecular sequencing based on any information besides the fact that this is a nonsquamous non—small cell lung cancer. Current NCCN guidelines recommending molecular testing for patients regardless of gender, ethnicity, or smoking history. The fact that she is a nonsmoker is important but is not in the prerequisite for us to start doing molecular testing for non–small cell lung cancer patients. Currently,ALKrearrangement happens in approximately 5% of patients with non—small cell lung cancer.

Transcript edited for clarity.

Case: A 50-Year-Old Woman WithALK-Rearranged NSCLC

• A 50-year-old woman first presented with symptoms of dyspnea, persistent cough with bloody sputum, and intermittent right-sided chest pain
• Relevant PMH:
  • Nonsmoker, had childhood exposure to second-hand smoke
  • No history or presence of pneumonia or bronchitis
  • No history of diabetes, cardiovascular disease, or renal disease
• Diagnostic workup:
  • CT of the chest showed right lung mass
  • Biopsy confirmed NSCLC (adenocarcinoma) in right lung
  • MRI showed scattered small brain lesions. Patient is asymptomatic
  • Molecular testing:
    • EGFR and KRASWT
    • IHC:ALK-rearrangement
• Treatment: started on crizotinib; achieved a confirmed partial response including CNS response
• At 12-month follow-up, disease progression seen in the right lung mass, with 2 new liver lesions and progression in the brain
  • Mutation analysis;ALK I1171Nresistance mutation
• She was started on brigatinib 90 mg once daily and tolerated the dose well; after 1 week, her dose was increased to 180 mg once daily (2 90-mg tablets)
  • Had some mild nausea and diarrhea, but continued treatment
  • Achieved partial response, including reduction in CNS and liver lesions
  • At 15-month follow-up, now with stable disease