of ALK-positive non-small cell lung cancer (NCSLC). However, head-tohead comparisons between most available ALK inhibitors are lacking. The objective of this study was to conduct a systematic literature review (SLR) and meta-analyses to estimate the relative efficacy of brigatinib compared to other approved ALK inhibitors or chemotherapy in patients with locally advanced or metastatic ALK inhibitornaïve ALK-positive NSCLC (1 prior chemotherapy regimen was allowed). Methods: An SLR was conducted following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Searches (from inception to August 1, 2019) were performed in MEDLINE, Embase, the Cochrane Library and key conference proceedings (2016)(2017)(2018)(2019) to identify relevant phase II or III randomized controlled trials (RCTs) in ALK inhibitor-naïve ALK-positive NSCLC patients. Bayesian network meta-analyses (NMAs) and Bucher indirect treatment comparisons (ITCs) were performed using fixed and random effects models to assess the comparative efficacy and safety of brigatinib with other ALK inhibitors or chemotherapy as 1L treatment. Results: The SLR identified 8 RCTs assessing alectinib, brigatinib, ceritinib, crizotinib, and chemotherapy in the 1L setting, of which 5 global trials (ALEX, ALTA-1L, ASCEND-4, PROFILE 1007, PROFILE 1014) were included. The base-case, fixed effects results demonstrated that brigatinib significantly reduced the risk of disease progression or death (independent review committee [IRC]-assessed progression-free survival [PFS]) compared with ceritinib (HR, 0.42; 95% confidence interval [CI], 0.26-0.67), crizotinib (HR, 0.49; 95% CI, 0.35-0.68), and chemotherapy (HR, 0.23; 95% CI, 0.16-0.34). No significant differences were observed between brigatinib and alectinib in IRC-assessed (HR, 0.98; 95% CI, 0.61-1.57) or investigator-assessed PFS (HR, 1.01; 95% CI, 0.64-1.58) for overall patients, and in investigator-assessed PFS (HR, 0.63 95% CI, 0.28-1.42) for the subgroup with baseline CNS metastases. There were also no significant differences between brigatinib and all comparators for overall survival. Subgroup analyses of patients who had not received prior chemotherapy yielded similar results (Table 1).
Conclusion:Brigatinib significantly prolonged PFS in ALK inhibitornaïve patients with ALK-positive NSCLC compared with ceritinib, crizotinib, and chemotherapy and was at least as effective as alectinib in reducing the risk of progression, suggesting that brigatinib is an effective 1L treatment. The results also suggest strong efficacy of brigatinib in patients with CNS metastases.