Abstract
Simple SummaryThe treatment of anaplastic lymphoma kinase (ALK) rearrangement-positive (ALK-p) advanced non-small cell lung cancer (NSCLC) remains a challenge. We compared the safety and efficacy of lorlatinib and alectinib in patients with ALK-p ALK-inhibitor‒naïve advanced NSCLC (in overall participants and in the Asian and non-Asian subgroups). The results showed that in the overall participant group, the efficacy of lorlatinib and alectinib was not significantly different in terms of progression-free survival (PFS) and overall survival (OS). Although in the Asian subgroup, PFS was not significantly different upon treatment with lorlatinib or alectinib, in the non-Asian subgroup, PFS was significantly better in response to lorlatinib than with alectinib. Grade 3 or higher adverse events in the overall participant group were significantly more frequent with lorlatinib than with alectinib. These results will provide valuable information that would enable the improvement of treatment strategies for ALK-p ALK-inhibitor‒naïve advanced NSCLC.To date, there have been no head-to-head randomized controlled trials (RCTs) comparing the safety and efficacy of lorlatinib and alectinib in anaplastic lymphoma kinase (ALK) rearrangement-positive (ALK-p) ALK-inhibitor‒naïve advanced non-small cell lung cancer (NSCLC). We performed a network meta-analysis comparing six treatment arms (lorlatinib, brigatinib, alectinib, ceritinib, crizotinib, and platinum-based chemotherapy) in overall participants and in Asian and non-Asian subgroups. Primary endpoints were progression-free survival (PFS), overall survival (OS), and grade 3 or higher adverse events (G3-AEs). There were no significant differences between lorlatinib and alectinib in overall participants for both PFS (hazard ratio [HR], 0.742; 95% credible interval [CrI], 0.466–1.180) and OS (HR, 1.180; 95% CrI, 0.590–2.354). In the Asian subgroup, there were no significant differences in PFS between lorlatinib and alectinib (HR, 1.423; 95% CrI, 0.748–2.708); however, in the non-Asian subgroup, PFS was significantly better with lorlatinib than with alectinib (HR, 0.388; 95% CrI, 0.195–0.769). The incidence of G3-AEs in overall participants was significantly higher with lorlatinib than with alectinib (risk ratio, 1.918; 95% CrI, 1.486–2.475). These results provide valuable information regarding the safety and efficacy of lorlatinib in ALK-p ALK-inhibitor‒naïve advanced NSCLC. Larger head-to-head RCTs are needed to validate the study results.
Highlights
Studies conducted in the field of molecular biology over the past decade have contributed substantially to a better understanding of the molecular mechanisms underlying the development and progression of non-small cell lung cancer (NSCLC) [1,2]
After adopting the PICOS approach, a total of eight studies were selected for the network meta-analysis (NMA) analysis; two studies that compared crizotinib with chemotherapy (PROFILE1014 [60], PROFILE1029 [61]), three studies that compared alectinib with crizotinib (ALEX [22], J-ALEX [23], and ALESIA [62]), and one study each that compared ceritinib with chemotherapy, brigatinib with crizotinib, and lorlatinib with crizotinib (ACEND-4 [63], ALTA-1L [64], and CROWN [33], respectively)
This systematic review and NMA compared the efficacy and safety of lorlatinib and alectinib in anaplastic lymphoma kinase (ALK)-p and ALK inhibitor-naïve NSCLC patients according to the best practice guidelines
Summary
Studies conducted in the field of molecular biology over the past decade have contributed substantially to a better understanding of the molecular mechanisms underlying the development and progression of non-small cell lung cancer (NSCLC) [1,2]. This has enabled remarkable progress in the development of treatment strategies for NSCLC, which accounts for 84% of all lung cancers [1,2,3]. The overall five-year survival rate of localized lung cancer is 63%. There has always been a need for the constant improvement and development of therapeutic strategies
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