Clinical lung cancer · 2026
Comparative Effectiveness of First-Line Tyrosine Kinase Inhibitors in ALK-Positive Metastatic Non-Small Cell Lung Cancer by Presence of Brain Metastases.
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Ghosh Sharmistha, Chen Yuanbin, Le Hoa H, Ashaye Ajibade, Danes Christopher, Roney Kyle, LeMasters Traci, Chirikov Viktor, Lee Kyung Min, Kim Chul
Аннотация
PURPOSE: The study compared outcomes of anaplastic lymphoma kinase positive (ALK+) metastatic non-small cell lung cancer (mNSCLC) patients treated with first-line (1L) tyrosine kinase inhibitors (TKIs) as monotherapy.
METHODS: This retrospective cohort study (January 2016-June 2024) used Komodo Healthcare Map claims to analyze ALK+ mNSCLC patients treated with 1L ALK TKIs by presence of brain metastasis (BM). Multivariable and propensity score (PS)-weighted Cox proportional hazards regressions compared 1L ALK TKI cohorts for treatment discontinuation (TTD), time to next treatment (TTNT), and overall survival (OS): alectinib, brigatinib, lorlatinib versus crizotinib; brigatinib versus alectinib; brigatinib versus lorlatinib. Patterns of full-prescribing dose achievement and dose reduction were examined descriptively.
RESULTS: A total of 1623 patients received 1L alectinib (n = 1100), brigatinib (n = 58), crizotinib (n = 384) or lorlatinib (n = 81). Alectinib, brigatinib, and lorlatinib all had significant adjusted hazard ratios (HRs) for TTD and TTNT versus crizotinib, overall and within BM subgroups. PS-weighted HRs for 1L brigatinib versus alectinib/1L brigatinib versus lorlatinib were: TTD: 0.85 (0.56-1.28)/0.93 (0.49-1.76); TTNT: 0.94 (0.60-1.48)/1.46 (0.64-3.32); OS: 0.86 (0.44-1.70)/1.41 (0.41-4.84). Full prescribing dose was achieved by 97% of alectinib, 89% of brigatinib, and 70% of lorlatinib patients (P < .001); 79%, 78%, 65%, respectively, were still on full prescribing dose by 12 months of treatment (P = .01).
CONCLUSIONS: There was no statistically significant difference in TTD, TTNT, OS for brigatinib versus alectinib and lorlatinib; however, the small brigatinib and lorlatinib samples limit statistical power. More patients on 1L alectinib or brigatinib achieved full prescribing dose and stayed on it for longer compared to those on 1L lorlatinib.
METHODS: This retrospective cohort study (January 2016-June 2024) used Komodo Healthcare Map claims to analyze ALK+ mNSCLC patients treated with 1L ALK TKIs by presence of brain metastasis (BM). Multivariable and propensity score (PS)-weighted Cox proportional hazards regressions compared 1L ALK TKI cohorts for treatment discontinuation (TTD), time to next treatment (TTNT), and overall survival (OS): alectinib, brigatinib, lorlatinib versus crizotinib; brigatinib versus alectinib; brigatinib versus lorlatinib. Patterns of full-prescribing dose achievement and dose reduction were examined descriptively.
RESULTS: A total of 1623 patients received 1L alectinib (n = 1100), brigatinib (n = 58), crizotinib (n = 384) or lorlatinib (n = 81). Alectinib, brigatinib, and lorlatinib all had significant adjusted hazard ratios (HRs) for TTD and TTNT versus crizotinib, overall and within BM subgroups. PS-weighted HRs for 1L brigatinib versus alectinib/1L brigatinib versus lorlatinib were: TTD: 0.85 (0.56-1.28)/0.93 (0.49-1.76); TTNT: 0.94 (0.60-1.48)/1.46 (0.64-3.32); OS: 0.86 (0.44-1.70)/1.41 (0.41-4.84). Full prescribing dose was achieved by 97% of alectinib, 89% of brigatinib, and 70% of lorlatinib patients (P < .001); 79%, 78%, 65%, respectively, were still on full prescribing dose by 12 months of treatment (P = .01).
CONCLUSIONS: There was no statistically significant difference in TTD, TTNT, OS for brigatinib versus alectinib and lorlatinib; however, the small brigatinib and lorlatinib samples limit statistical power. More patients on 1L alectinib or brigatinib achieved full prescribing dose and stayed on it for longer compared to those on 1L lorlatinib.