Avapritinib in Advanced Gastrointestinal Stromal Tumor: Case Series and Review of the Literature From a Tertiary Care Center in India

Figures & data

Figure 1. Response to imatinib, sunitinib and regorafenib therapy in case 1.

¹⁸F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) done post imatinib, sunitinib and regorafenib therapy in patient A. (A) maximum intensity projection, (B, C & D) axial contrast enhanced CT and (E, F & G) fused PET/CT images showing multiple solid cystic masses with increased FDG uptake in the enhancing solid component (arrows) suggestive of metabolically active liver metastases. Follow-up ¹⁸F-FDG PET/CT done 3 months after initiation of avapritinib therapy, which revealed resolution of metabolic activity in the corresponding lesions (H–N) with hypodense/cystic changes in the previously enhancing lesions, suggestive of complete metabolic response.

Figure 2. Response to avapritinib therapy in case 1.

^{1 8}F-FDG positron emission tomography/computed tomography (PET/CT) done 6 months after avapritinib therapy in patient A. (A) Maximum intensity projection, (B, C & D) axial contrast enhanced CT and (E, F & G) fused PET/CT images shows increase in size of the liver lesions with FDG avid enhancing areas in the periphery of the lesion (arrows), suggestive of progressive disease.

Figure 3. Subdural haemorrhage in case 2.

Computed tomography head of patient B showing biconcave hyperdensity in the right parieto-occipital location with associated midline shift suggestive of subdural hemorrhage.

Figure 4. Response to imatinib in case 5.

(1A) Axial computed tomography abdomen of patient E showing a heterogenous mass measuring 7.1 × 6.6 cm in the surgical bed in the gastro-hepatic region and a hypodense lesion in segment IVB of liver (1B) measuring1.5 × 1.8 cm. (2A) Axial CT abdomen of first follow-up scan showing a heterogenous mass measuring10.2 × 10.7 cm in the surgical bed in the gastro-hepatic region and a hypodense lesion in segment IVB of the liver measuring 2.9 × 2.8cm (2B), suggestive of disease progression.

Figure 5. Response to avapritinib in case 5.

(3A) In a patient with PDGFRA D842V mutation (patient E), maximum intensity projection image of ¹⁸F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) showing physiologic biodistribution in the brain, liver, kidneys and urinary bladder. (3B) Axial CT abdomen showing a heterogenous mass measuring 5.5 × 6.0 cm in the surgical bed in the gastro-hepatic region and a hypodense lesion in the segment IVB of the liver 2.1 × 2.0 cm with no significant FDG uptake in any of the lesions on fused PET-CT images, suggestive of partial response (3C).

Table 1. Base line characteristics of patients.

	Primary site of tumor	Age (years)/sex	Mutation	Response to imatinib	Response to sunitinib	Response to regorafenib	Other treatments tried	Sites of metastasis
A	Jejunum	28/male	c-KIT exon 17	PR	PD	PD	Progressed on immunotherapy	Liver, omental, serosa
B	Duodenum	49/male	c-KIT exon 11	PR	PD	PD	Progressed on immunotherapy	Liver, omental, serosa, bone, nodes
C	Stomach	40/male	c-KIT exon 9	PR	PD	PR		Liver, omental, bone
D	Duodenum	60/female	Not known	PR	PD	PD	Progressed on pazopanib	Liver, omental, serosa
E	Stomach	76/male	PDGFRA D842V	PD	Could not tolerate	PR		Liver, serosa

PD: Progressive disease; PDGFRA: Platelet-derived growth factor alpha; PR: Partial response; SD: Stable disease.

Table 2. Avapritinib characteristics including response rates, progression free time, outcomes and toxicities.

	Dose	Response	Progression-free time	Outcomes	Toxicities
A	300 mg	Initial SD at 3 months followed by PD at 6 months	6 months	On ripretinib	Grade 3 rash, greying of hair, grade 2 hyperbilirubinemia, grade 2 anemia
B	300 mg	Initial PR at 2 months, SD at 5 months followed by PD at 8 months	8 months	Planned for ripretinib	Grade 2 rash, periorbital puffiness, grade 4 SDH
C	300 mg	PD	5 months	Planned for ripretinib	Grade 2 rash
D	300 mg	Not available	1 months	Death	Grade 2 hyperbilirubinemia
E	300 mg	PR	3 months	On avapritinib	Periorbital puffiness, pleural effusion

PD: Progressive disease; PR: Partial response; SD: Stable disease; SDH: Subdural hemorrhage.

Figure 6. Progression-free survival.