Pexidartinib (PLX3397), a CSF1R/KIT/FLT3 inhibitor, is FDA-approved (August 2019) for adu...
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BMA-CSF1R-TGCT |
|---|---|
| Type | Actionability |
| Status | reviewed 2026-05-04 | pending_clinical_signoff | actionability review required |
| Diseases | DIS-TGCT |
| Sources | SRC-ESMO-SARCOMA-2024 SRC-ILLUMINATE-TAP-2019 SRC-NCCN-SARCOMA |
Actionability Facts
| Biomarker | BIO-CSF1R |
|---|---|
| Variant | CSF1R pathway activation — diffuse-type TGCT (COL6A3-CSF1 fusion OR CSF1 overexpression; pexidartinib indication does not require molecular confirmation of fusion) |
| Disease | DIS-TGCT |
| ESCAT tier | IA |
| Recommended combinations | pexidartinib 400 mg PO BID (with food; REMS enrollment required; baseline LFTs, monthly monitoring for first 8 weeks, then every 3 months) |
| Contraindicated monotherapy | pexidartinib in patients with pre-existing hepatic impairment (Child-Pugh B/C) or significant baseline transaminase elevation — hepatotoxicity risk |
| Evidence summary | Pexidartinib (PLX3397), a CSF1R/KIT/FLT3 inhibitor, is FDA-approved (August 2019) for adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations not amenable to improvement with surgery. ILLUMINATE phase III trial (Tap et al., Lancet 2019): N=120 (pexidartinib vs placebo, crossover design); primary endpoint ORR at week 25 by RECIST 1.1 and TTP-MRI. ORR: 38% (RECIST) vs 0% placebo (p<0.0001); 56% by TTP-MRI vs 0%. mDOR: not reached at median 23.1 months follow-up. Clinical benefit rate: 56%. Safety: significant hepatotoxicity (cholestatic hepatitis, including one fatal case in open-label extension); ALT/AST elevations in ~51%; FDA REMS program mandatory. EMA approved for same indication (2020). No biomarker companion diagnostic required — all TGCT patients are eligible based on clinical criteria (symptomatic, surgery-resistant). CSF1R IHC or COL6A3-CSF1 fusion testing is not required for treatment initiation. |
Notes
ESCAT IA (FDA-approved, phase III RCT). REMS program: pexidartinib is dispensed only through certified pharmacies; prescribers must be enrolled. Hepatotoxicity monitoring: LFTs at baseline, weekly for 8 weeks, then every 2–3 weeks for 2 months, then monthly. If ALT/AST >5× ULN, hold and reassess; if cholestatic pattern (elevated ALP + bilirubin), discontinue permanently — one fatal cholestatic hepatitis case occurred in the open-label extension. Differentiate from other CSF1R-directed agents used for tumor-associated macrophage depletion (emactuzumab, cabiralizumab) which are investigational for solid tumors — those are off-label and not approved. Surgery remains first-line; pexidartinib is reserved for patients where surgery cannot adequately control disease.
Used By
No reverse references found in the YAML corpus.