Treatment Regimen for Patients With ALK+ Non-Small Cell Lung Cancer - Episode 2
Jonathan W. Riess, MD, MS:My initial impressions of this patient are that she has stage 4 nonsmall cell lung cancer, adenocarcinoma. PD-L1 expression was negative at 0%. Her next-generation sequencing panel was positive for anALKtranslocation, and this is very important. Patients who present withALK-positive lung cancer can often present in this way. They’re also more like to have effusions, like pleural effusions and pericardial effusions. The mainstay of treatment for these patients are ALK tyrosine kinase inhibitors. The patient was started on crizotinib, which was the initial ALK inhibitor that was approved to treat metastaticALK-rearranged nonsmall cell lung cancer, which has a median progression-free survival in clinical trials of about 9 to 10 months.
However, there are newer next-generation ALK inhibitors, including brigatinib and alectinib, that have been developed. And more recently, alectinib has been approved for first-line treatment ofALK-rearranged nonsmall cell lung cancer based on comparison between alectinib and crizotinib in the ALEX trial, with recently updated progression-free survival data that showed progression-free survival in excess of 30 months on average. So, that’s very exciting and a game changer for the treatment of these patients.
If I diagnosed this patient today, I would start the patient on alectinib as first-line therapy for her stage 4ALK-rearranged lung cancer, and that’s based upon 2 clinical large phase III clinical trials: the J-ALEX study conducted in Japan and the ALEX study conducted in the United States and Europe, which showed a progression-free survival benefit that was dramatic between alectinib and crizotinib. This was updated to show a median progression-free survival in the ALEX study of more than 30 months compared with about 10 months on crizotinib. So, a dramatic improvement. And that improvement’s driven mainly by its excellent bloodbrain barrier penetration that can induce intracranial responses and actually help forestall the development of, and prevent, brain metastases. So, that’s one of the main differences between alectinib and crizotinib, and really helps underlie that benefit, so that’s very exciting.
And you can see that when the patient relapsed, she had intracranial metastatic disease. And you know that’s something that could be, more often than not, delayed or forestalled with alectinib.
Transcript edited for clarity.
CASE:ALK+ NonSmall Cell Lung Cancer