Lung cancer (Amsterdam, Netherlands) · 2026
Comparative efficacy of taletrectinib versus first-generation TKIs in TKI-naïve ROS1+ non-small cell lung cancer: A matching-adjusted indirect comparison.
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Nagasaka Misako, Liu Geoffrey, Pérol Maurice, Chen Wenfeng, Bazhenova Lyudmila, Zhou Caicun
Аннотация
BACKGROUND: Taletrectinib is a next-generation, selective ROS1 tyrosine kinase inhibitor (TKI) approved for the treatment of advanced ROS1+ non-small cell lung cancer (NSCLC). In the absence of head-to-head trials comparing ROS1 TKIs, we aimed to compare the efficacy of taletrectinib with first-generation TKIs, crizotinib and entrectinib, in TKI-naïve patients with ROS1+ NSCLC using an unanchored matching-adjusted indirect comparison.
METHODS: Selected baseline covariates were used for adjustment between pooled taletrectinib data from the TRUST-I (NCT04395677) and TRUST-II (NCT04919811) studies and published data from the registrational crizotinib and entrectinib studies. A descriptive cross-trial comparison of safety for treatment-related adverse events (TRAEs) was also conducted.
RESULTS: After adjustment for baseline covariates, taletrectinib was associated with significantly higher odds of objective response versus crizotinib or entrectinib, significantly longer duration of response versus entrectinib (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.21-0.60), significantly longer progression-free survival versus crizotinib (HR, 0.48; 95% CI, 0.27-0.88) or entrectinib (HR, 0.42; 95% CI, 0.27-0.65), and significantly longer overall survival versus crizotinib (HR, 0.34; 95% CI, 0.15-0.77) or entrectinib (HR, 0.48; 95% CI, 0.27-0.88). Results across sensitivity analyses consistently favored taletrectinib versus crizotinib or entrectinib. In a descriptive safety comparison, there were no marked differences in TRAE rates across taletrectinib, crizotinib, and entrectinib.
CONCLUSIONS: In this analysis, taletrectinib was associated with more favorable response and survival outcomes compared with crizotinib or entrectinib in TKI-naïve patients with ROS1+ NSCLC after adjustment for baseline characteristics, supporting taletrectinib as an effective treatment option in this patient population.
METHODS: Selected baseline covariates were used for adjustment between pooled taletrectinib data from the TRUST-I (NCT04395677) and TRUST-II (NCT04919811) studies and published data from the registrational crizotinib and entrectinib studies. A descriptive cross-trial comparison of safety for treatment-related adverse events (TRAEs) was also conducted.
RESULTS: After adjustment for baseline covariates, taletrectinib was associated with significantly higher odds of objective response versus crizotinib or entrectinib, significantly longer duration of response versus entrectinib (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.21-0.60), significantly longer progression-free survival versus crizotinib (HR, 0.48; 95% CI, 0.27-0.88) or entrectinib (HR, 0.42; 95% CI, 0.27-0.65), and significantly longer overall survival versus crizotinib (HR, 0.34; 95% CI, 0.15-0.77) or entrectinib (HR, 0.48; 95% CI, 0.27-0.88). Results across sensitivity analyses consistently favored taletrectinib versus crizotinib or entrectinib. In a descriptive safety comparison, there were no marked differences in TRAE rates across taletrectinib, crizotinib, and entrectinib.
CONCLUSIONS: In this analysis, taletrectinib was associated with more favorable response and survival outcomes compared with crizotinib or entrectinib in TKI-naïve patients with ROS1+ NSCLC after adjustment for baseline characteristics, supporting taletrectinib as an effective treatment option in this patient population.