PDGFRA D842V in GIST is imatinib-RESISTANT (distinct from imatinib-sensitive PDGFRA non-D...
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| ID | BMA-PDGFRA-D842V-GIST |
|---|---|
| Tipo | Relevância terapêutica |
| Estado | reviewed 2026-04-27 | pending_clinical_signoff | actionability review required |
| Doenças | DIS-GIST |
| Fontes | SRC-CIVIC SRC-FDA-CDS-2026 SRC-NCCN-MELANOMA-2025 |
Fatos de ação
| Biomarcador | BIO-PDGFRA |
|---|---|
| Variante | D842V (alça de ativação, exon 18 — ~7% do GIST, predominantemente gástrico) |
| Doença | DIS-GIST |
| Nível ESCAT | IA |
| Combinações recomendadas | avapritinib em monoterapia (1L para o GIST avançado D842V — independentemente da linha) |
| Contraindicated monotherapy | imatinib (D842V resistant), sunitinib (D842V resistant), regorafenib (D842V resistant), ripretinib (modest activity in D842V; reserve for avapritinib failure) |
| Resumo das provas | PDGFRA D842V in GIST is imatinib-RESISTANT (distinct from imatinib-sensitive PDGFRA non-D842V mutations). Avapritinib (NAVIGATOR phase 1/2 + VOYAGER phase 3, Heinrich Lancet Oncol 2020 / Kang JCO 2022 — ORR 88-91% in D842V GIST; treatment-naive cohort) is FDA-approved for advanced D842V GIST. Imatinib, sunitinib, regorafenib are ineffective. |
Notas
ESCAT IA. OncoKB Level 1. Source-gap: SRC-NCCN-SARCOMA / SRC-NCCN-GIST-2025 / SRC-NAVIGATOR / SRC-VOYAGER not yet ingested. CNS toxicity (cognitive effects, intracranial hemorrhage) is on-target / dose- related — dose modifications standard. Companion-diagnostic genotyping via NGS panel mandatory before avapritinib initiation. Adjuvant imatinib has NO benefit in D842V GIST — these patients should be observed post-resection.
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Não há referências reversas encontradas no corpus YAML.