PDGFRA D842V in GIST is imatinib-RESISTANT (distinct from imatinib-sensitive PDGFRA non-D...
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BMA-PDGFRA-D842V-GIST |
|---|---|
| Type | Actionability |
| Status | reviewed 2026-04-27 | pending_clinical_signoff | actionability review required |
| Diseases | DIS-GIST |
| Sources | SRC-CIVIC SRC-FDA-CDS-2026 SRC-NCCN-MELANOMA-2025 |
Actionability Facts
| Biomarker | BIO-PDGFRA |
|---|---|
| Variant | D842V (activation loop, exon 18 — ~7% of GIST, predominantly gastric) |
| Disease | DIS-GIST |
| ESCAT tier | IA |
| Recommended combinations | avapritinib monotherapy (1L for advanced D842V GIST — irrespective of line) |
| Contraindicated monotherapy | imatinib (D842V resistant), sunitinib (D842V resistant), regorafenib (D842V resistant), ripretinib (modest activity in D842V; reserve for avapritinib failure) |
| Evidence summary | 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. |
Notes
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.
Used By
No reverse references found in the YAML corpus.