Pralsetinib (Selective RET TKI): ctDNA Clearance Flags 12-mo + PFS in RET-Fusion NSCLC

Pralsetinib, an oral CNS-penetrant RET tyrosine-kinase inhibitor, was evaluated in a single-arm prospective biomarker study of 21 Chinese patients with advanced RET-fusion NSCLC (Phase 2 ARROW, NCT03037385). Baseline PIK3CA co-mutation slashed median PFS to 3.0 vs 12.4 months, while low baseline ctDNA across three metrics (allele-freq HR 0.24; cfDNA-normalized HR 0.20; methylation HR 0.09) and week-8 ctDNA clearance drove PFS not reached vs 4.8 mo and disease-control 71% vs 0%. Safety was not detailed here, but the 281-pt global ARROW update reports grade ≥3 neutropenia 18% and only 7% treatment discontinuations; the 12-month PFS in ctDNA-low/cleared patients aligns with the ARROW first-line median PFS ~13 mo, suggesting ctDNA stratifies who actually enjoys that benefit.