Brigatinib trumps crizotinib in treatment of advanced NSCLC
The anaplastic lymphoma kinase (ALK) inhibitor brigatinib demonstrated better progression-free survival (PFS) vs crizotinib among ALK-positive non-small-cell lung cancer (NSCLC) patients not previously treated with an ALK inhibitor.
The results of the ALTA-1L (ALK in Lung Cancer Trial of Brigatinib in 1st Line) trial, presented at the International Association for the Study of Lung Cancer (IASLC) 19th World Conference on Lung Cancer (WCLC 2018), showed that ALK-positive NSCLC patients who received brigatinib experienced better PFS vs those who received crizotinib (median PFS, not reached vs 9.8 months; hazard ratio [HR] for disease progression or death, 0.49; 95 percent confidence interval [CI], 0.33 to 0.74; p=0.0007). [N Engl J Med 2018, doi: 10.1056/NEJMoa1810171]
The phase III, open-label, randomized, multicentre study, where 275 participants were followed up for 9−11 months, also demonstrated PFS in favour of brigatinib across all study subgroups, including patients who had received prior chemotherapy (27 percent of the population; HR, 0.35; 95 percent CI, 0.14 to 0.85; p=0.0207).
“Brigatinib has demonstrated broad preclinical activity against ALK resistance mutations and is the only ALK inhibitor to also demonstrate activity against multiple EGFR-mutant cells lines. Moreover, it has demonstrated high systemic and excellent central nervous system [CNS] penetration, and the longest reported median PFS for any ALK inhibitor,” commented trial investigator Dr Ross Camidge from the University of Colorado Cancer Center, Aurora, Colorado, US.
More patients in the crizotinib arm experienced events vs those who received brigatinib (46 percent vs 26 percent). The overall survival (OS) data of the study are still immature up to the present time.
The median duration of response was also longer in the brigatinib group vs the crizotinib group (not reached vs 11.1 months), with a higher proportion of patients in the brigatinib group maintaining response at 12 months vs the crizotinib group (75 percent [95 percent CI, 63 to 83] vs 41 percent [95 percent CI, 26 to 54]).
“Among patients with measurable CNS lesions, those who received brigatinib showed a higher intracranial response rate vs those who received crizotinib [78 prercent vs 29 percent; odds ratio (OR), 10.42; 95 percent CI, 1.9 to 57.05; p=0.0028],” emphasized Camidge.
”For patients with any brain metastases at baseline, those who received brigatinib also fared better than those who received crizotinib [OR, 13; 95 percent CI, 4.38 to 38.61; p<0.0001],” he added.
About a quarter of patients receiving brigatinib had their doses reduced mainly due to increased serum creatine phosphokinase, amylase and lipase. However, there were no reported clinical cases of pancreatitis. Other adverse events (AEs) that resulted in dose reduction in less than 2 percent of cases include increased serum transaminases, pneumonitis and rash.
“Since most of these AEs may be due to ‘paper toxicities’ where the clinical impact is not well-understood, we need to be sure that these dose reductions are appropriate and not potentially compromising efficacy,” commented discussant Dr Fiona Blackhall from the University of Manchester, UK.