AVAPRITINIB TAB

Clinical Criteria Summary

Mutational testing shows platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation insensitive to imatinib including PDGFRA D842V
Progressive disease on prior trials of imatinib, sunitinib, regorafenib AND dose-escalated ripretinib

Prescribed and monitored by a VA / VA Community Care oncologist
Goals of care and role of Palliative Care consult have been discussed and documented

For patients who can become pregnant or whose partners can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception
For patients who are breastfeeding/lactating: Advised to avoid providing breastmilk during therapy and for 2 weeks after the final dose

Platelet count < 50 × 109/L
Unmanageable drug-drug interaction
Pregnancy
Lactating
Inclusion Criteria (All must be met)
Documented diagnosis of one of the following subtypes of advanced systemic mastocytosis: aggressive systemic mastocytosis, systemic mastocytosis with an associated hematologic neoplasm, or mast cell leukemia
Prescribed and monitored by a VA / VA Community Care hematologist / oncologist
Goals of care and role of Palliative Care consult have been discussed and documented
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 3
Additional Inclusion Criteria (Select if appropriate)
For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception
For patients who are breastfeeding/lactating: Advised to avoid providing breastmilk during therapy and for 2 weeks after the final dose

For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception.
For patients who are breastfeeding/lactating: Advised to avoid providing breastmilk during therapy and for 2 weeks after the final dose.

Adults with unresectable or metastatic GIST (umGIST) harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations
Unresectable or metastatic GISTs harboring PDGFRA exon 18 mutations insensitive to imatinib including PDGFRA D842V

First-line therapy for unresectable, progressive, or advanced/metastatic GISTs (upmGISTs; amGIST) with PDGFRA exon 18 D842V mutation
Additional (5th-line) option after progression on approved therapies (imatinib, sunitinib, regorafenib, ripretinib) for upmGISTs with sensitive mutations excluding PDGFRA exon 18 mutations that are insensitive to imatinib including D842V
Progressive GIST after trials of imatinib and 3 other kinase inhibitors such as sunitinib, regorafenib, and dose-escalated ripretinib

No boxed warnings or contraindications
Monitor for intracranial hemorrhage (ICH), cognitive effects (e.g., memory impairment, amnesia, somnolence, speech disorder), photosensitivity, and embryofetal toxicity
Avoid strong CYP3A inhibitors; avoid or reduce dose for moderate CYP3A inhibitors; avoid strong or moderate CYP3A inducers

FDA: 1st-line therapy for umGIST with PDGFRA exon 18 mutations including recurrent GIST post-resection
NCCN: Preferred (1st-line) option for unresectable, progressive, or advanced/metastatic GISTs with PDGFRA exon 18 D842V mutation; may be considered for neoadjuvant therapy of localized GIST with PDGFRA D842V mutation
ESMO: Standard 1st-line therapy for recurrent GIST post-resection or metastatic GISTs with PDGFRA exon 18 D842V mutation; may be considered for neoadjuvant therapy of localized GIST with PDGFRA D842V mutation

Advanced Systemic Mastocytosis (AdvSM): Treatment of adults with AdvSM, including aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL).
Indolent Systemic Mastocytosis (ISM): Treatment of adults with ISM.

Not recommended for treatment of patients with platelet count (PLT) < 50 × 109/L.
VA formulary use is restricted to:
AdvSM (ASM, SM-AHN, or MCL) with PLT ≥ 50 × 109/L
Symptomatic ISM with PLT ≥ 50 × 109/L in patients with an absolute contraindication or unmanageable intolerance to midostaurin.

AdvSM: 200 mg PO QD; continue treatment until disease progression or unacceptable toxicity.
ISM: 25 mg PO QD.
Dosage modifications are indicated for adverse reactions, strong or moderate CYP3A inhibitors, and severe hepatic impairment.

Boxed Warnings: None.
Contraindications: None.
Other Warnings/Precautions: Intracranial hemorrhage, cognitive effects, photosensitivity, embryofetal toxicity.
Drug Interactions: Avoid strong CYP3A inhibitors; avoid or reduce dose with moderate CYP3A inhibitors; avoid strong or moderate CYP3A inducers.