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RET fusion in advanced NSCLC (~1-2% of adenocarcinoma): selpercatinib (LIBRETTO-001 Drilo...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

IDBMA-RET-FUSION-NSCLC
TypeActionability
Statusreviewed 2026-04-27 | pending_clinical_signoff | actionability review required
DiseasesDIS-NSCLC
SourcesSRC-CIVIC SRC-ESMO-NSCLC-METASTATIC-2024 SRC-NCCN-NSCLC-2025

Actionability Facts

BiomarkerBIO-RET
Variantfusion (gene-level — KIF5B-RET, CCDC6-RET, NCOA4-RET et al.)
DiseaseDIS-NSCLC
ESCAT tierIA
Recommended combinationsselpercatinib monotherapy (1L preferred per LIBRETTO-431), pralsetinib monotherapy
Contraindicated monotherapycabozantinib / vandetanib (inferior to selective RET-TKIs in NSCLC)
Evidence summaryRET fusion in advanced NSCLC (~1-2% of adenocarcinoma): selpercatinib (LIBRETTO-001 Drilon 2020 — ORR 64% prior-tx / 85% TKI-naive; LIBRETTO-431 1L vs platinum-pemetrexed) and pralsetinib (ARROW Gainor 2021 — ORR 70%) are highly selective RET-TKIs with deep, durable responses including in CNS. Multikinase TKIs (cabozantinib, vandetanib) are inferior and toxic.

Notes

ESCAT IA. OncoKB Level 1. Detection: RNA-NGS preferred over DNA-NGS (intronic breakpoints). KIF5B-RET most common partner (~70%); fusion-partner generally does not influence TKI response (unlike ALK). Trial-source gaps: SRC-LIBRETTO001-DRILON-2020, SRC-LIBRETTO-431, SRC-ARROW not yet ingested.

Used By

No reverse references found in the YAML corpus.