TriangleHEALTH PROFESSIONAL · SOURCE READING
Avapritinib
Source: Gastrointestinal Stromal Tumors Treatment (PDQ®)–Health Professional Version, National Cancer Institute.
Source updated: December 13, 2024 · Captured 2026-09-09.
Selected source text with whitespace normalised. This Triangle page is not an NCI PDQ summary.
Patients with GISTs that harbor a PDGFRA exon 18 D842V variant should initially be given avapritinib. However, for patients whose GISTs are asymptomatic or indolent, a period of observation is reasonable to avoid treatment toxicities.
Evidence (avapritinib in patients with a PDGFRA D842V variant):
NAVIGATOR (NCT02508532) was a phase I, single-arm, open-label trial of 56 patients with a PDGFRA D842V variant. Patients received avapritinib at a daily dose of either 300 mg or 400 mg.[2][Level of evidence C3]
Source links and citations
NAVIGATOR (NCT02508532) was a phase I, single-arm, open-label trial of 56 patients with a PDGFRA D842V variant. Patients received avapritinib at a daily dose of either 300 mg or 400 mg.[2][Level of evidence C3]
An overall response was seen in 49 of 56 patients (88%) (95% confidence interval [CI], 76%–95%), with five patients (9%) achieving a complete response.
NAVIGATOR (NCT02508532) was a phase I, single-arm, open-label trial of 56 patients with a PDGFRA D842V variant. Patients received avapritinib at a daily dose of either 300 mg or 400 mg.[2][Level of evidence C3]
The 1-year PFS rate was 81% (95% CI, 67%–94%) and the 1-year duration of response was 70% (95% CI, 54%–87%).
NAVIGATOR (NCT02508532) was a phase I, single-arm, open-label trial of 56 patients with a PDGFRA D842V variant. Patients received avapritinib at a daily dose of either 300 mg or 400 mg.[2][Level of evidence C3]
At median follow-up of 15.9 months, the estimated 1-year OS rate was 91%, and the estimated 2-year OS rate was 81%.
NAVIGATOR (NCT02508532) was a phase I, single-arm, open-label trial of 56 patients with a PDGFRA D842V variant. Patients received avapritinib at a daily dose of either 300 mg or 400 mg.[2][Level of evidence C3]
The high overall response rate results of the NAVIGATOR trial led the U.S. Food and Drug Administration (FDA) to approve avapritinib for patients with GISTs with a PDGFRA exon 18 variant, including D842V variants.
Evidence (avapritinib in patients who did not respond to imatinib and at least one additional TKI):
VOYAGER (NCT03465722) was a phase III open-label trial of 476 patients with advanced GISTs that did not respond to imatinib and at least one additional TKI. Patients were randomly assigned to receive either avapritinib 300 mg daily (n = 240) or regorafenib 160 mg daily (3-weeks-on/1-week-off regimen) (n = 236), with crossover allowed from regorafenib to avapritinib.[28]
VOYAGER (NCT03465722) was a phase III open-label trial of 476 patients with advanced GISTs that did not respond to imatinib and at least one additional TKI. Patients were randomly assigned to receive either avapritinib 300 mg daily (n = 240) or regorafenib 160 mg daily (3-weeks-on/1-week-off regimen) (n = 236), with crossover allowed from regorafenib to avapritinib.[28]
The median PFS was 4.2 months in the avapritinib arm and 5.6 months in the regorafenib arm (hazard ratio [HR], 1.25; 95% CI, 0.99–1.57; P = .055). Among patients without a PDGFRA D842V variant, the median PFS was 3.9 months in the avapritinib arm and 5.6 months in the regorafenib arm (HR, 1.34; 95% CI, 1.06–1.69; P = .012).[28][Level of evidence B1]
Source links and citations
VOYAGER (NCT03465722) was a phase III open-label trial of 476 patients with advanced GISTs that did not respond to imatinib and at least one additional TKI. Patients were randomly assigned to receive either avapritinib 300 mg daily (n = 240) or regorafenib 160 mg daily (3-weeks-on/1-week-off regimen) (n = 236), with crossover allowed from regorafenib to avapritinib.[28]
OS data were immature at the time of the report with no interval differences noted between the study arms.
VOYAGER (NCT03465722) was a phase III open-label trial of 476 patients with advanced GISTs that did not respond to imatinib and at least one additional TKI. Patients were randomly assigned to receive either avapritinib 300 mg daily (n = 240) or regorafenib 160 mg daily (3-weeks-on/1-week-off regimen) (n = 236), with crossover allowed from regorafenib to avapritinib.[28]
Overall and grade 3 or higher treatment-related adverse events did not differ between groups. However, cognitive effects occurred more often in patients who received avapritinib (25.9%) than in patients who received regorafenib (3.8%).
VOYAGER (NCT03465722) was a phase III open-label trial of 476 patients with advanced GISTs that did not respond to imatinib and at least one additional TKI. Patients were randomly assigned to receive either avapritinib 300 mg daily (n = 240) or regorafenib 160 mg daily (3-weeks-on/1-week-off regimen) (n = 236), with crossover allowed from regorafenib to avapritinib.[28]
Because avapritinib did not improve PFS or OS compared with regorafenib in the treated population, it is not indicated until patients have failed multiple previous TKI therapies (outside of its specific variant indication above).
If indicated, avapritinib is given at 300 mg daily. Avapritinib is teratogenic, and thus, warrants effective contraception during and up to 6 weeks after the final dose.[29] The 300 mg dose was generally well-tolerated in the phase I NAVIGATOR study, with grade 3 to 4 toxicities including anemia, hyperbilirubinemia, fatigue, abdominal pain, diarrhea, peripheral edema, pleural effusion, and cognitive impairment.[2]
Cognitive effects must be closely monitored, with treatment changes (reductions, modifications, discontinuation) made promptly. Based on a post-hoc analysis of patients receiving 300 mg daily, grade 1 to 2 cognitive effects were seen in 37% of patients and 52% of patients older than 65 years. These effects included cognitive impairment, mood changes, sleep disorder, dizziness, hallucinations, and intracranial hemorrhage. These cognitive effects generally improved once treatment changes were made.[29]
Source links and citations
Of note, for patients with GISTs who do not harbor a PDGFRA D842V variant, avapritinib should not be used until imatinib and at least two additional agents (sunitinib and regorafenib) are tried. The open-label phase III VOYAGER trial demonstrated that regorafenib improved PFS more than avapritinib in patients without a PDGFRA D842V variant.[28]
Source links and citations
Studies cited in this source section
Source citation is not a determination that a study applies to you.
Publication references
Read the original reference and check its publication notices.
Preserved source evidence · Not medical advice