Relapsed ALK-Rearranged NSCLC - Episode 1

Impressions of a Woman With ALK+ NSCLC

September 16, 2019

Robert C. Doebele, MD, PhD:The first case is a 53-year-old woman who presents with cough, shortness of breath, and hemoptysis, as well as pain in the right side of her chest. She really has no significant past medical history. She’s a never-smoker, although she was exposed to some secondhand smoke as a child, but she has no other significant comorbidities.

On physical examination, there were no remarkable findings. Her lungs were clear, and she had no other abnormal findings.

Her diagnostic work-up included a chest x-ray showing multiple opacities in the right lung. This was followed by a chest, abdomen, and pelvis CT [computed tomography] scan, which redemonstrated several lung nodules in the right lung. A brain MRI [magnetic resonance imaging] was performed and unfortunately showed extensive metastatic disease.

A biopsy of 1 of the right lung nodules was positive for lung adenocarcinoma. This was subsequently sent off for molecular testing, which includedEGFR,HER2,BRAF,KRAS,RET, andROS1FISH [fluorescence in situ hybridization]. Those were all negative. AnALKIHC [immunohistochemistry] was notably positive, and a PD-L1 [programmed death-ligand 1] score of 20% was observed.

I would say that there is no typicalALK-positive patient. This is a woman of middle age—a 53-year-old woman. She’s a never-smoker. And while we considerALK-positivity to be associated with never-smokers, which is statistically true, it’s really important to note that patients who are former or current smokers can also beALK-positive. So the testing of all patients with lung adenocarcinoma and non—small cell lung cancer is important because we identifyALK-positivity rarely in squamous cell and other histologies. Although there is this conventional wisdom that patients who areALK-positive are younger and are never-smokers, that shouldn’t prevent testing of older patients who are also smokers and have other histologies.

Fortunately, the prognosis forALK-positive patients is now quite good. We know from several long-term retrospective analyses that the overall survival forALK-positive patients can easily stretch into years and, in some cases, well over 5 years. This has really changed the way we think about certain patients with lung adenocarcinoma, especially those with genetic drivers such as anALKrearrangement. Because there are so many effective therapies, these patients often do well and lead a relatively normal life for many years.

Transcript edited for clarity.


Case: A 53-Year-Old Woman WithALK-Rearranged NSCLC

  • A 53-year-old woman presented with dyspnea, persistent cough with bloody sputum, and intermittent pain in right side of her chest
  • 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
  • PE: lungs, clear; no palpable masses or visible lesions; patient is of average height and weight, appears physically fit
  • Diagnostic workup:
    • Chest X-Ray: revealed multiple small solid lesions in right lung
    • CT with contrast chest/abdomen/pelvis: several hyperattenuated tumors in right lung
    • Biopsy confirmed lung adenocarcinoma
    • Molecular testing:
      • Genetic testing;EGFR, BRAF, RET,KRAS, HER2wild-type,ROS1FISH
      • IHC;ALK-rearrangement
      • PD-L1 TPS; 20%
    • Brain MRI: revealed extensive CNS involvement
  • Treatment:
    • Started on alectinib; achieved partial response
    • Developed fatigue, grade 1 constipation, and nausea; continued treatment
    • Imaging at 12 months showed disease progression
    • Tumor testing of a lung lesions demonstrated MET FISH+
  • She was started on crizotinib
    • Imaging at 3 and 6 months showed a partial response
    • Developed grade 2 diarrhea and visual disturbance; continued treatment
    • Imaging at 10 months showed progression in the CNS lesions and the lung
    • Repeat biopsy of the lung lesions and genotyping showed ALK L1196M mutation
  • She was started on brigatinib at 90 mg once daily; she tolerated therapy well and after 1 week, dose was increased to 180 mg once daily
    • Achieved partial response, including in CNS metastases
    • Had fatigue, but was able to resume some exercise
    • Remains on treatment 16 months later