Comparative efficacy of taletrectinib versus first-generation TKIs in TKI-naïve ROS1+ non-small cell lung cancer: A matching-adjusted indirect comparison.

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.