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ALK-Positive Non-Small Cell Lung Cancer Case Presentation
The Journal of Clinical Pathways invited Dr Mark Socinski, Executive Medical Director of the AdventHealth Cancer Institute in Orlando, Florida, to discuss clinical pathways and how his institution uses them to treat patients with ALK-positive non–small cell lung cancer.
The below case study has been edited for clarity.
Dr Socinski: Let's walk through a case of a patient with newly diagnosed stage IV non–small cell lung cancer who has an ALK fusion. The ALK population tends to be a little bit younger; the median age is in the mid-50s, and it’s about equal between men and women. So, let's say he is a 55-year-old gentleman, never-smoker, who presents with increased cough and shortness of breath. He gets a chest x-ray, which would be the typical first thing that we would do, and he has a right-sided pleural effusion. He goes on to get a chest computed tomography scan and in addition to the pleural fluid, he has a right upper lobe mass, and he has several nodules both in the right as well as the left lung. Because of the fluid and because of the nodules in the left lung, he would be considered stage IV.
We would typically do a positron emission tomography scan as well as brain magnetic resonance imaging (MRI). So, let's say that this gentleman has three subcentimeter lesions in the brain consistent with metastatic disease, which is a very typical finding in the ALK population. There's no edema associated with them on the brain MRI, there are no neurologic symptoms that the patient tells you, and he has a totally normal neurologic exam. The first thing is we have to make the diagnosis, and there are several options here. Typically, we would drain the pleural fluid and if there were cells in the pleural fluid, we would make the diagnosis of that.
It would be the standard of care to do genomic testing. In this patient, I typically would test whatever tissue we got, whether that's pleural fluid or a lung biopsy. But I would also do plasma-based testing, which I think has significant clinical utility in this setting. And I actually do both at the time of diagnosis because we know that doing both does increase the yield of finding one of these fusions or mutations that we act on. There are now nine or ten biomarkers that have Food and Drug Administration–approved therapies. The reason that these are FDA-approved therapies is that most of these are significantly more efficacious than either chemotherapy or immunotherapy. In fact, the ALK population is not particularly benefitted by immunotherapy in general. So, this patient does have stage IV disease, and let's say we do molecular testing on the pleural fluid and a plasma-based testing, and he's found to have an ALK fusion.
The fusion partner is EML4, which is the most common partner we see, so then we would have to make a therapeutic decision. We do know from a number of the initial profile trials that giving an ALK inhibitor, which happened to be crizotinib in those trials, was better than chemotherapy.
And then we saw the real ALK inhibitor drugs come in—drugs like alectinib, brigatinib, lorlatinib, and ceritinib. And all of these drugs were approved because they were better than crizotinib in randomized trials. Now, what happened first is that the ALEX trial, which tested alectinib vs crizotinib, was the first bit of information that we had with regard to a true ALK inhibitor. And alectinib was superior to crizotinib.
So, AdventHealth Cancer Institute replaced crizotinib with alectinib on our pathway because it was more efficacious, and there was really no significant cost difference between those two drugs. Thus, alectinib became the number-one pathway choice for a patient with stage IV disease like the patient we described. It also has very good central nervous system activity. The fact that this gentleman has three small, asymptomatic, nonthreatening lesions and no associated cerebral edema means I would feel very comfortable treating him with the drug alectinib, which is an oral capsule or tablet; it would be quite effective in the brain.
Now, the situation in ALK is that we've had several other first-line indications, most notably brigatinib in the ALTA-1L trial and lorlatinib in the CROWN trial. All of these are approved in the first-line setting, but we put them to the test in the pathway. At this point we've had discussions principally about brigatinib as well as lorlatinib concerning the basic principles of the clinical pathway, which is: Are those drugs more efficacious than alectinib? Currently, alectinib has retained its position as the pathway choice, and that's on the pathway at this particular point, despite the fact that we have a couple other ALK inhibitors.
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