• Karen L Reckamp, Huamao M Lin, Holly Cranmer, Yanyu Wu, Pingkuan Zhang, Stephen Kay, Laura J Walton, Junwu Shen, Sanjay Popat, and D Ross Camidge.
• Division of Medical Oncology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
• Curr Med Res Opin. 2022 Sep 1; 38 (9): 158715931587-1593.

BackgroundSecond-generation anaplastic lymphoma kinase (ALK) gene targeted tyrosine kinase inhibitors (TKIs) alectinib and brigatinib have shown efficacy as front-line treatments for ALK-positive non-small cell lung cancer (NSCLC). No head-to-head data are currently available for brigatinib vs alectinib in the ALK-TKI-naive population.ObjectiveTo estimate the relative overall survival (OS) for brigatinib vs alectinib with indirect treatment comparisons (ITCs) using ALEX and ALTA-1L clinical trial data.MethodsThe latest aggregate data from the ALEX trial and final patient-level data from ALTA-1L were used. ITCs were conducted with/without treatment crossover adjustments to estimate relative OS. Bucher methods, anchored matching-adjusted indirect comparisons (MAICs) and unanchored MAICs were employed in ITCs without treatment crossover adjustments. An inverse probability of censoring weight Cox model, a marginal structure model and rank-preserving structural failure time models (with/without re-censoring) within an anchored MAIC were used in ITCs with treatment crossover adjustments. Hazard ratios (HRs) and 95% confidence intervals (CIs) were reported.ResultsHRs for brigatinib vs alectinib for relative OS generated from ITCs without treatment crossover adjustments ranged from 0.90 (95% CI: 0.59-1.38) in the unanchored MAIC to 1.20 (95% CI: 0.69-2.11) using the Bucher method. Methods employing treatment switching adjustments estimated HRs for relative OS ranging from 0.74 (95% CI: 0.38-1.45) to 1.11 (95% CI: 0.63-1.94). Results from all ITCs did not indicate statistically different survival profiles.ConclusionRegardless of ITC methodology, OS is comparable for brigatinib vs alectinib in patients with ALK+ NSCLC previously untreated with an ALK inhibitor.

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