Relapsed ALK-Rearranged NSCLC - Episode 1
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 agea 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 nonsmall 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