Pexidartinib (PLX3397), a CSF1R/KIT/FLT3 inhibitor, is FDA-approved (August 2019) for adu...
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| ID | BMA-CSF1R-TGCT |
|---|---|
| Тип | Клінічна застосовність |
| Статус | переглянуто 2026-05-04 | очікує клінічного підпису | потрібне рев’ю клінічної застосовності |
| Хвороби | DIS-TGCT |
| Джерела | SRC-ESMO-SARCOMA-2024 SRC-ILLUMINATE-TAP-2019 SRC-NCCN-SARCOMA |
Дані про клінічну застосовність
| Біомаркер | BIO-CSF1R |
|---|---|
| Варіант | CSF1R pathway activation — diffuse-type TGCT (COL6A3-CSF1 fusion OR CSF1 overexpression; pexidartinib indication does not require molecular confirmation of fusion) |
| Хвороба | DIS-TGCT |
| Рівень ESCAT | IA |
| Рекомендовані комбінації | pexidartinib 400 mg PO BID (with food; REMS enrollment required; baseline LFTs, monthly monitoring for first 8 weeks, then every 3 months) |
| Протипоказана монотерапія | pexidartinib in patients with pre-existing hepatic impairment (Child-Pugh B/C) or significant baseline transaminase elevation — hepatotoxicity risk |
| Підсумок доказів | 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. |
Нотатки
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.
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