Brigatinib outplays crizotinib in ALK inhibitor-naïve advanced NSCLC
medwireNews: Treatment with brigatinib is associated with better outcomes than crizotinib in patients with anaplastic lymphoma kinase (ALK) translocation-positive advanced non-small-cell lung cancer (NSCLC) who have not received prior ALK-targeted therapy, indicate phase III trial results.
In the ALTA-1L study of patients who had received one prior systemic treatment (but not an ALK inhibitor) for locally advanced or metastatic disease, treatment with brigatinib at a dose of 90 mg/day for the first week and 180 mg/day thereafter led to a significant improvement in the primary endpoint of progression-free survival (PFS), as assessed by blinded independent-review, relative to crizotinib 250 mg twice a day.
Specifically, the risk for progression or death was a significant 51% lower with brigatinib, while PFS at 12 months was achieved by 67% of 137 brigatinib-treated patients and 43% of the 138 given crizotinib, a significant difference.
Speaking to medwireNews, lead author D Ross Camidge (University of Colorado Cancer Center, Aurora, USA) commented that “despite only 9–11 months of follow-up across the two arms, brigatinib has already convincingly beaten crizotinib.”
The improvement in PFS with brigatinib was significant across almost all subgroups, and was “particularly pronounced” among patients with baseline central nervous system (CNS) metastases, with an 80% reduced risk for progression or death in the brigatinib versus crizotinib arm, noted Camidge.
And although the risk reduction associated with brigatinib treatment was not significant in patients without baseline brain metastases, the study authors believe that “this interim analysis may emphasize differences in early progression.”
They write in The New England Journal of Medicine: “Because of the known poor efficacy of crizotinib in the CNS, CNS progression events may tend to have an earlier onset than other events; therefore, differences in early progression-free survival will be most apparent among patients with baseline brain disease.”
Brigatinib treatment also boosted the confirmed objective response rate, at 71% versus 60% with crizotinib, and the confirmed intracranial response rate in patients with measurable baseline CNS metastases, at 78% versus 29%.
Overall survival at 1 year was comparable between the brigatinib and crizotinib groups (85 vs 86%), but the investigators acknowledge that these data “will be confounded by crossover of patients in the crizotinib group to brigatinib during the trial and subsequent use of other tyrosine kinase inhibitors after discontinuation of the trial by patients from either group.”
The team believes, however, that “[w]ith further follow-up, data in both groups will mature and help to better contextualize the role of brigatinib as compared with other next-generation ALK inhibitors.”
And indeed, Camidge noted that head-to-head comparisons of brigatinib and the other next-generation ALK inhibitor with a first-line license, alectinib, are currently underway in the post-crizotinib setting, and should help build a good efficacy and safety comparison to aid physicians in deciding which drug to use.
“While a head-to-head first-line trial now sounds attractive, that would take years to read out given the tremendous benefit we are seeing with these drugs,” he said.
These ALTA-1L results were simultaneously presented at the International Association for the Study of Lung Cancer 19th World Conference on Lung Cancer in Toronto, Ontario, Canada.
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