Patients are frequently young, fit, and never smokers.
With ALK inhibitors survival is now measured in years and is associated with preserved quality-of-life.
Approximately 4-5% of patients with NSCLC have ALK positive disease.
Drug resistance is inevitable and patients eventually succumb to the disease.
There are three generations of ALK tyrosine kinase inhibitors available.
ALK fusions are present in 3-7% of NSCLCs.
Associated with adenocarcinoma histology.
Have a predilection for brain metastasis and CNS disease reported in approximately one fifth patients at diagnosis and up to 3/4 of patients throughout the disease course.
Later generations of tyrosine kinase inhibitors have enabled greater CNS penetrability, efficacy and protection from progression of a relapsing disease.
Next generation ALK tyrosine kinase inhibitors including alectinib , ceritinib, and Brigatinib have generally replaced the first generation TKI crizotinib as first line treatment for patients with ALK positive NSCLC.
Molecular therapies with first, second, and third generation ALK inhibitors have improved patient survival measured in years, and preserved quality-of-life.
Drug resistance is presently inevitable and patients with advanced disease eventually succumb.
Current recommended adjuvant treatment for a patient with resected ALK positive. NSCLC is platinum-based combination chemotherapy, however, risk recurrence is high with a five-year recurrence rate or death ranging from 45% for stage 1B disease to 76% prestige III disease.
Five-year survival ranges from 71% per stage IB disease to 36% for stage IIIA disease.
Among patients with resected, ALK positive NSCLC of stage, IB II or IIIA adjuvant alectinib significantly improved disease free survival as compared with platinum-based chemotherapy (ALINA investigators.).