Taletrectinib (next-gen ROS1 TKI) linked to better PFS/OS than crizotinib/entrectinib in ROS1+ NSCLC (MAIC)

Taletrectinib is a next-generation, selective ROS1 tyrosine kinase inhibitor (TKI) evaluated here via an unanchored matching-adjusted indirect comparison (MAIC) using pooled, single-arm TRUST-I (NCT04395677) and TRUST-II (NCT04919811) data versus published single-arm registrational studies of first-generation ROS1 TKIs crizotinib and entrectinib in TKI-naïve ROS1+ advanced NSCLC (sample size and absolute ORR/PFS/OS not reported in the abstract). After covariate adjustment, taletrectinib showed higher odds of objective response vs both comparators and longer time-to-event outcomes: duration of response vs entrectinib (HR 0.35, 95% CI 0.21-0.60), PFS vs crizotinib (HR 0.48, 95% CI 0.27-0.88) or entrectinib (HR 0.42, 95% CI 0.27-0.65), and OS vs crizotinib (HR 0.34, 95% CI 0.15-0.77) or entrectinib (HR 0.48, 95% CI 0.27-0.88). Safety was compared descriptively with “no marked differences” in treatment-related AE rates across agents; for benchmark context, historical first-line crizotinib single-arm data in ROS1+ NSCLC report ORR ~72% and median PFS ~15.9-19.2 months (cross-trial comparisons are inherently shaky, especially with evolving CNS management and post-progression sequencing).