First-Line Alectinib vs. Brigatinib in Advanced Non–Small Cell Lung Cancer with ALK Rearrangement: Real-World Data

Abstract

Purpose Alectinib and brigatinib are second-generation anaplastic lymphoma receptor tyrosine kinases (ALKs) that are widely used as first-line therapy for treating ALK-positive advanced non–small cell lung cancer (NSCLC). Given the lack of a head-to-head comparison of these drugs as first-line therapies, this retrospective observational study aimed to compare the real-world efficacy and safety of alectinib and brigatinib.Materials and Methods Patients who received alectinib or brigatinib as the first-line treatment for ALK-positive advanced NSCLC were evaluated for clinical outcomes of objective response rate (ORR), intracranial ORR, time to next treatment (TTNT), progression-free survival (PFS), overall survival (OS), and safety profiles.Results Of 208 patients who received either alectinib or brigatinib as a first-line treatment, 176 received alectinib and 32 received brigatinib. At the data cutoff point, the median follow-up duration was 16.5 months (95% confidence interval [CI], 14.7 to 18.3) in the brigatinib group and 27.5 months (95% CI, 24.6 to 30.4) in the alectinib group. The ORR was 92.5% with alectinib and 93.8% for brigatinib. The intracranial ORR rates were 92.7% (38/41) and 100% (10/10), respectively. The rate of PFS at 12 months was comparable between the alectinib group and the brigatinib groups (84.4% vs. 84.1%, p=0.64), and the median TTNT, PFS, and OS were not reached in either group. Treatment-related adverse events were usually mild, and treatment discontinuation due to adverse events was rare (alectinib 4.5% vs. brigatinib 6.25%).Conclusion Alectinib and brigatinib had similar clinical benefits when used as the first-line treatment of NSCLC patients with ALK rearrangement in the real world.

Bridging the Gap between Trial Adverse Events and Real-World Data

“…We congratulate Jeon et al [ 1 ] for their thorough analysis comparing alectinib and brigatinib as first-line therapies for advanced non–small cell lung cancer (NSCLC) with anaplastic lymphoma receptor tyrosine kinase ( ALK ) rearrangement in a real-world context. This study provided valuable information that both drugs are highly effective and generally well tolerated with mild side effects.…”

“…The study by Jeon et al [ 1 ] predominantly focuses on AE profiles of alectinib with a limited exploration of those associated with brigatinib, such as hypertension, diarrhea and increased blood creatine phosphokinase, amylase, and lipase [ 2 ]. Although ALK inhibitors generally share similar safety concerns, the literature indicates that each may have a unique safety profile.…”

“…Such investigations will not only broaden our understanding of AEs associated with first-line ALK inhibitors but also lead to better strategies for managing AEs that may occur during treatment. While Jeon et al’s research [ 1 ] significantly adds to our comprehension of ALK inhibitors in treating ALK-positive NSCLC, a pressing need remains for future research into the real-world AEs of these drugs, which may enable healthcare professionals to provide more effective patient care, ultimately leading to favorable treatment outcomes.…”