Abstract
To date, no head-to-head trials have compared the efficacy of brigatinib and alectinib against anaplastic lymphoma kinase (ALK) rearrangement-positive (ALK-p), ALK-inhibitor-naïve, advanced non-small cell lung cancer (NSCLC) with central nervous system (CNS) metastasis. We conducted an indirect treatment comparison (ITC) between brigatinib and alectinib, with crizotinib as a common comparator, using a Bayesian model with non-informative prior distribution and assessed the between-study heterogeneity of the studies. The primary efficacy endpoint was progression-free survival (PFS), and efficacy was ranked using the surface under the cumulative ranking (SUCRA) curve values. ITC analysis showed that there were no significant differences in PFS between the brigatinib and alectinib arms. However, the SUCRA values revealed that alectinib ranked the highest by efficacy in the overall patient population, whereas brigatinib ranked the highest by efficacy in the CNS metastasis sub-group. Although there were no significant differences in the incidence of G3–5 adverse events between the brigatinib and alectinib arms in the overall patient population, the data were deemed insufficient for the CNS metastasis sub-group analysis. This study provides critical information to clinicians regarding the efficacy of brigatinib for ALK-p, ALK-inhibitor-naïve, advanced NSCLC patients, with and without CNS metastasis. Larger randomized, controlled trials are warranted to confirm our results.
Highlights
Basic, clinical, and translational research conducted over the last 10 years has enhanced our understanding of the molecular disease mechanisms of non-small cell lung cancer (NSCLC)
The adoption of the PICOS approach led to the retention of two studies, one of which compared brigatinib with crizotinib (ALTA-1L) [23], and the other two compared alectinib and crizotinib (ALEX and J-ALEX) [19,20] for the indirect treatment comparison (ITC) analysis
In a sub-analysis of central nervous system (CNS) metastasis cases, there was no significant difference between brigatinib and alectinib, with hazard ratio (HR) (95% credible intervals (CrIs)) of 0.561 (0.195 to 1.284), surface under the cumulative ranking (SUCRA) was higher for brigatinib (SUCRA = 96.3) compared to for alectinib (SUCRA = 53.8)
Summary
Clinical, and translational research conducted over the last 10 years has enhanced our understanding of the molecular disease mechanisms of non-small cell lung cancer (NSCLC). The treatment strategy for NSCLC patients has undergone a remarkable evolution [1,2]. Lung cancer remains the leading cause of cancer-related deaths worldwide. In 2018, lung cancer accounted for 13% of all cancer cases, with a 5-year relative survival rate of only 18% [3]. 16% of cases are diagnosed at a localized stage, at which the 5-year survival rate is 56%. Most lung cancers are diagnosed at an advanced stage, at which the 5-year survival rate is only 5% [3,4]
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