ALTArnative ALK-inhibitor.

Targeted Therapy: Brigatinib, a next-generation ALK-targeted tyrosine kinase inhibitor.
The Trial: Crizotinib had a good run, but it’s already failed to match results of the second-generation alectinib. Now brigatinib takes it on head-to-head in the phase 3 ALTA-1L trial. 275 patients with ALK-rearranged non-small cell lung cancer (NSCLC) naive to ALK-inhibition were randomized to crizotinib versus brigatinib until toxicity or progression. The primary endpoint of progression-free survival was significantly improved at one year with brigatinib (67%) verusus crizotinib (43%). And as demonstrated previously, the rate of intracranial response among those with asymptomatic brain mets ≥1 cm (n=39) was quite a bit higher with brigatinib (14 of 18) than with crizotinib (6 of 21). Among those with asymptomatic brain mets of any size (n=81), the hazard ratio for progression or death with brigatinib versus crizotinib was a striking 0.20.
The Takeaway: Both brigatinib and alectinib seem to be better at controlling systemic and intracranial ALK-rearranged NSCLC than their predecessor crizotinib. | Camidge, N Engl J Med 2018


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