Real-world treatment patterns and time-to-treatment discontinuation among advanced ALK-positive non-small cell lung cancer patients.

Abstract

8603 Background: Advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) is typically treated with ALK tyrosine kinase inhibitors (TKIs) in the first-line (1L) setting. While clinical trials provide efficacy data, real-world evidence on treatment patterns and time-to-treatment discontinuation or death (TTD) remains scarce. Such evidence may better inform modern clinical practice and decision-making regarding long-term treatment planning and sequencing decisions. Methods: This retrospective observational cohort study analyzed patients with advanced ALK+ NSCLC in the Optum Clinformatics Data Mart (2016–2021). Eligible patients were ≥18 years of age, with ≥6 months of continuous enrollment prior to the index date, a lung cancer diagnosis identified via ICD-10 codes, and ≥1 prescription fill for an ALK TKI. Outcomes included TTD for 1L and second-line (2L) therapies, assessed using the Kaplan-Meier (KM) method. Treatment patterns, including discontinuation rates and transitions to 2L therapy, were also evaluated. Results: Among 680 patients, 1L therapy distribution was as follows: crizotinib (n=366, 53.8%), alectinib (n=267, 39.3%), brigatinib (n=22, 3.2%), and ceritinib (n=25, 3.7%). Lorlatinib (n=16) was excluded from the analysis due to its atypical use in 1L during the study period, potentially reflecting unique clinical scenarios. The median TTD for 1L therapy was 8.3 months overall (95% CI: 6.7–9.7). TTD by therapy was as follows: alectinib, 15.3 months (95% CI: 11.0–21.4); brigatinib, 7.8 months (95% CI: 3.6–18.1); ceritinib, 7.6 months (95% CI: 4.3–23.5); crizotinib, 5.7 months (95% CI: 4.7–6.8). Only 168 (24.7%) patients transitioned to another ALK TKI in 2L, with alectinib being the most common among 1L crizotinib recipients, and lorlatinib being the most common among 1L alectinib and brigatinib recipients. Median TTD for 2L therapies was 8.0 (95% CI: 5.7-11.7) months overall. Conclusions: This study provides real-world evidence on TTD and treatment patterns among advanced ALK+ NSCLC patients. Transition rates to 2L ALK TKIs were lower than expected based on clinical trials, with high rates of discontinuation without transition. With alectinib, brigatinib, and lorlatinib equally recommended as 1L options in US clinical guidelines, these findings provide real-world evidence to help clinicians differentiate among therapies and guide treatment sequencing decisions. 1L ALK TKI (n) Transition to 2L ALK TKI (%) Median 1L TTD (Months, 95% CI) Alectinib (267) 51 (19.1%) 15.3 (11.0–21.4) Brigatinib (22) 2 (9.1%) 7.8 (3.6–18.1) Ceritinib (25) 14 (56.0%) 7.6 (4.3–23.5) Crizotinib (366) 101 (27.6%) 5.7 (4.7–6.8) Overall (680) 168 (24.7%) 8.3 (6.7–9.7) 1L first-line, 2L second-line, ALK anaplastic lymphoma kinase, TKI tyrosine kinase inhibitor, TTD time-to-treatment discontinuation or death, CI confidence interval.