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    BIOMARKER:

    PDGFRA D842V

    i
    Other names: Platelet Derived Growth Factor Receptor Alpha, Platelet-Derived Growth Factor Receptor Alpha Polypeptide, Alpha-Type Platelet-Derived Growth Factor Receptor, CD140 Antigen-Like Family Member A, CD140a Antigen, PDGF-R-Alpha, PDGFR-2, PDGFR2, Alpha Platelet-Derived Growth Factor Receptor, Platelet-Derived Growth Factor Alpha Receptor, PDGFR-Alpha, RHEPDGFRA, CD140A
    Entrez ID:
    5156
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    Related tests:
    17d
    Imatinib TDM in GIST (clinicaltrials.gov)
    P2, N=28, Recruiting, Reema A. Patel | Not yet recruiting --> Recruiting | Trial primary completion date: Dec 2024 --> Dec 2025
    Enrollment open • Trial primary completion date • Stroma
    |
    KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    KIT mutation • PDGFRA D842V • PDGFRA mutation
    |
    imatinib
    2ms
    DS-6157a in Participants With Advanced Gastrointestinal Stromal Tumor (GIST) (clinicaltrials.gov)
    P1, N=34, Terminated, Daiichi Sankyo | Completed --> Terminated; The study was terminated due to a business decision.
    Trial termination • Stroma • Metastases
    |
    KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • GPR20 (G Protein-Coupled Receptor 20)
    |
    KIT mutation • PDGFRA D842V • PDGFRA mutation
    |
    DS-6157
    3ms
    Testing the Use of Nilotinib and Paclitaxel as a Treatment for Patients With Prior Taxane Treatment, A ComboMATCH Treatment Trial (clinicaltrials.gov)
    P2, N=40, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended
    Trial suspension
    |
    PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    PDGFRA D842V • KIT L576P • KIT K642E • KIT V559 • KIT V559A • KIT W557
    |
    paclitaxel • Tasigna (nilotinib)
    3ms
    Avapritinib-based SAR studies unveil a binding pocket in KIT and PDGFRA. (PubMed, Nat Commun)
    Against this background, we solve the crystal structures of avapritinib in complex with wild-type and mutant PDGFRA and stem cell factor receptor (KIT), which provide evidence and understanding of inhibitor binding and lead to the identification of a sub-pocket (Gα-pocket). We utilize this information to design, synthesize and characterize avapritinib derivatives for the determination of key pharmacophoric features to overcome drug resistance and limit potential blood-brain barrier penetration.
    Journal
    |
    KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    PDGFRA D842V • PDGFRA mutation • PDGFR wild-type
    |
    Ayvakit (avapritinib)
    4ms
    AVIATOR2020: French Long Term Registry With Longitudinal Follow up of PDGFRA D842V-GIST Patients (clinicaltrials.gov)
    P=N/A, N=25, Active, not recruiting, Centre Leon Berard | Recruiting --> Active, not recruiting | N=45 --> 25 | Trial completion date: Apr 2025 --> Dec 2024 | Trial primary completion date: Apr 2023 --> Apr 2024
    Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date
    |
    PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    PDGFRA D842V
    |
    Ayvakit (avapritinib)
    5ms
    Esterase-Responsive Polyglycerol-Based Nanogels for Intracellular Drug Delivery in Rare Gastrointestinal Stromal Tumors. (PubMed, Pharmaceuticals (Basel))
    Cell viability and live cell imaging studies revealed that the loaded NGs are capable of intracellular drug release by showing similar IC values to those of the free drugs. Furthermore, multi-drug-loaded NGs were capable of overcoming BLU-285 resistance in T1-α-D842V + G680R cells, demonstrating the utility of this carrier system.
    Journal • Stroma
    |
    PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    KIT mutation • PDGFRA D842V • PDGFRA mutation
    |
    Ayvakit (avapritinib)
    6ms
    AZURE: Study of Elenestinib (BLU-263) in Advanced Systemic Mastocytosis (AdvSM) and and Other KIT Altered Hematologic Malignancies (clinicaltrials.gov)
    P1/2, N=67, Recruiting, Blueprint Medicines Corporation | Initiation date: Apr 2023 --> Sep 2023
    Trial initiation date • Combination therapy • Metastases
    |
    PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    KIT mutation • PDGFRA D842V • PDGFRA mutation • KIT D816V • KIT exon 17 mutation • PDGFRA fusion
    |
    azacitidine • elenestinib (BLU-263)
    6ms
    A COLLECTION OF PATIENT-DERIVED XENOGRAFT MODELS OF GASTROINTESTINAL STROMAL TUMORS (CTOS 2023)
    One model is characterized by an imatinib-resistant PDGFRA exon 18 p.D842V mutation... We are expanding our established platform of well-characterized GIST PDX models, that were proven to serve as an excellent tool for preclinical drug testing and tumor biology studies. The platform is available for cooperative projects with academic and commercial partners.
    Preclinical • Stroma
    |
    KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    KIT mutation • PDGFRA D842V • PDGFRA mutation • KIT exon 17 mutation • PDGFRA exon 18 mutation
    |
    imatinib
    8ms
    Testing the Use of Nilotinib and Paclitaxel as a Treatment for Patients With Prior Taxane Treatment, A ComboMATCH Treatment Trial (clinicaltrials.gov)
    P2, N=40, Recruiting, National Cancer Institute (NCI) | Initiation date: Sep 2023 --> Dec 2023
    Trial initiation date
    |
    PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    PDGFRA D842V • KIT L576P • KIT K642E • KIT V559 • KIT V559A • KIT W557
    |
    paclitaxel • Tasigna (nilotinib)
    8ms
    Evaluation of Systemic Treatment Options for Gastrointestinal Stromal Tumours. (PubMed, Cancers (Basel))
    An exception is represented by patients with tumours harbouring the imatinib-insensitive PDGFRA D842V mutation who would be better treated with avapritinib...While an increase in the dose of imatinib to 800 mg is an option for the second line, sunitinib is usually considered the standard of care...Regorafenib and ripretinib are the standards of care in the third and fourth lines, respectively. The recent development of various systemic treatment options allows for a more personalised approach based on the molecular profile of the GIST, patient characteristics, and the profile of medications' adverse events. A multidisciplinary approach is paramount since combining systemic treatment with locoregional treatment options and supportive care is vital for long-term survival.
    Review • Journal • Stroma
    |
    BRAF (B-raf proto-oncogene) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    BRAF mutation • KIT mutation • KIT exon 11 mutation • PDGFRA D842V • PDGFRA mutation
    |
    imatinib • Sutent (sunitinib) • Stivarga (regorafenib) • Ayvakit (avapritinib) • Qinlock (ripretinib)
    8ms
    Testing the Use of Nilotinib and Paclitaxel as a Treatment for Patients With Prior Taxane Treatment, A ComboMATCH Treatment Trial (clinicaltrials.gov)
    P2, N=40, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting
    Enrollment open
    |
    PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    PDGFRA D842V • KIT L576P • KIT K642E • KIT V559 • KIT V559A • KIT W557
    |
    paclitaxel • Tasigna (nilotinib)
    8ms
    REVISITING IN- AND OFF LABEL DRUGS FREQUENTLY USED IN METASTATIC GIST USING A BROAD IN VITRO PROFILING PANEL OF PRIMARY AND SECONDARY KIT AND PDGFRA-MUTANT GIST CELLS – CLINICAL IMPLICATIONS (CTOS 2023)
    Apart from approved drugs (imatinib, sunitinib, regorafenib, ripretinib, and avapritinib, we evaluated cabozantinib, pazopanib, dasatinib, and sorafenib... Preclinical testing suggests that dose-escalation of or retreatment with imatinib is not effective in exon 11 mutant GIST with secondary mutations. Pazopanib appears highly ineffective against any secondary mutation but shows notable activity in exon 9 mutant GIST. Cabozantinib is the only drug with strong activity against the gatekeeper T670I and the AL D820Y mutation.
    Preclinical • Metastases
    |
    KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    KIT mutation • PDGFRA D842V • PDGFRA mutation • KIT T670I
    |
    dasatinib • sorafenib • imatinib • Sutent (sunitinib) • Votrient (pazopanib) • Cabometyx (cabozantinib tablet) • Stivarga (regorafenib) • Ayvakit (avapritinib) • Qinlock (ripretinib)
    8ms
    PREDICTING IMATINIB RESPONSES USING IN VITRO MODELS OF PDGFRA-MUTANT GASTROINTESTINAL STROMAL TUMOR (CTOS 2023)
    If a patient progresses on imatinib, there are additional FDA-approved treatments (sunitinib, regorafenib, ripretinib), which are not currently available for those patients that progress on avapritinib. Our model has the potential to identify which PDGFRA exon 18 mutant GIST patients would benefit from front-line imatinib therapy, while subsequently identifying those that would require avapritinib treatment. Avapritinib was recently approved for first-line treatment for all PDGFRA exon 18 mutant GIST in the United States. Imatinib has been used clinically for over two decades, and is more cost-effective and has a superior safety and tolerability profile compared to avapritinib.
    Preclinical • Stroma
    |
    KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    PDGFRA D842V • PDGFRA mutation • PDGFRA exon 18 mutation
    |
    imatinib • Sutent (sunitinib) • Stivarga (regorafenib) • Ayvakit (avapritinib) • Qinlock (ripretinib)
    8ms
    EFFICACY OF RIPRETINIB IN A MULTICENTER EXPANDED ACCESS PROGRAM IN PATIENTS WITH ADVANCED GASTROINTESTINAL STROMAL TUMORS HARBOURING NON-KIT EXON 11 MUTATIONS. (CTOS 2023)
    Objective: There remains an unmet need for effective and well tolerated systemic therapy for metastatic gastrointestinal stromal tumors (GISTs) after disease progression on imatinib is challenging. In the real world setting, ripretinib has durable benefit in metastatic GISTs harbouring non KIT exon 11 primary mutations. Ripretinib at a dose of 150 mg BD can be safely administered. Ripretinib is generally well tolerated with toxicity profile consistent with previous reports.
    Clinical • Stroma • Metastases
    |
    KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    KIT exon 11 mutation • PDGFRA D842V • PDGFRA mutation • PDGFR wild-type
    |
    imatinib • Qinlock (ripretinib)
    8ms
    COMPREHENSIVE ANALYSIS OF THE GENOMIC LANDSCAPE AND CLINICAL BEHAVIOR IN GIST USING NEXT GENERATION SEQUENCING (NGS, MSK-IMPACT) (CTOS 2023)
    This study represents a one of the most comprehensive analyses of the genomic landscape and integration of genomic features with clinicopathologic attributes and survival outcome in GIST.
    Clinical • Tumor mutational burden • Next-generation sequencing
    |
    BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • TSC1 (TSC complex subunit 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • TNFRSF14 (TNF Receptor Superfamily Member 14) • GATA3 (GATA binding protein 3)
    |
    TP53 mutation • BRAF mutation • PIK3CA mutation • PTEN mutation • CDKN2A mutation • KIT exon 11 mutation • PDGFRA D842V • PDGFRA mutation • KIT exon 13 mutation • KIT exon 17 mutation • TSC1 mutation • KIT exon 17 mutation + KIT exon 18 mutation
    |
    MSK-IMPACT
    8ms
    GENOMIC ALTERATIONS IN ADVANCED GASTROINTESTINAL STROMAL TUMORS AS REVEALED BY COMPREHENSIVE GENOMIC PROFILING TESTS (CTOS 2023)
    Fifty-four patients (38%) underwent CGP tests using specimens obtained before initiating treatment with imatinib and 90 (63%) using specimens obtained after imatinib. The present study highlights that approximately 25% and 50% of patients in each KIT/PDGFRA and wild-type group exhibit targetable GAs, thereby illustrating the clinical utility of CGP tests in identifying therapeutic targets in advanced GISTs.
    Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • BRCA Biomarker • Stroma • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • PALB2 (Partner and localizer of BRCA2) • ETV6 (ETS Variant Transcription Factor 6) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • TSC1 (TSC complex subunit 1) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)
    |
    TP53 mutation • BRAF V600E • TMB-H • MSI-H/dMMR • HER-2 amplification • BRAF V600 • NTRK3 fusion • STK11 mutation • ETV6-NTRK3 fusion • PDGFRA D842V • PDGFRA mutation • TSC1 mutation • PDGFR wild-type
    |
    FoundationOne® CDx • OncoGuide™ NCC Oncopanel System
    |
    Keytruda (pembrolizumab) • Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • imatinib
    8ms
    KIT and PDGFRA Variants and the Survival of Patients with Gastrointestinal Stromal Tumor Treated with Adjuvant Imatinib. (PubMed, Cancers (Basel))
    Little evidence for OS benefit is available from randomized trials for patients whose GIST harbors KIT exon 9 mutation, KIT insertion mutation, PDGFRA D842V mutation, or lacks KIT and PDGFRA mutations. Adjuvant imatinib improves OS substantially if high-risk GISTs can be identified, treatment duration is long enough, and GISTs harbor an imatinib-sensitive mutation.
    Review • Journal • Stroma
    |
    KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    KIT mutation • KIT exon 11 mutation • KIT exon 9 mutation • PDGFRA D842V • PDGFRA mutation
    |
    imatinib
    9ms
    The landscape of PDGFRA mutation in Chinese patients with glioma (ESMO 2023)
    This type of mutation is mostly found in the non-tyrosine kinase domain. Investigating the PDGFRA map and PDGFRA inhibitors has significant exploratory value.
    Clinical
    |
    KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    PDGFRA D842V • PDGFRA mutation • KIT fusion • PDGFRA fusion
    9ms
    Deep learning predicts patients outcome and mutations from digitized histology slides in gastrointestinal stromal tumor. (PubMed, NPJ Precis Oncol)
    DL models yielded comparable results to the Miettinen classification for relapse-free-survival prediction in localized GIST without adjuvant Imatinib (C-index=0.83 in cross-validation and 0.72 for independent testing)...Additionally, novel histological criteria predictive of patients' outcome and mutations were identified by reviewing the tiles selected by the models. As a proof of concept, our study showed the possibility of implementing DL with digitized WSI and may represent a reproducible way to improve tailoring therapy and precision medicine for patients with GIST.
    Journal • Stroma
    |
    KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    KIT mutation • PDGFRA D842V • PDGFRA mutation • PDGFRA exon 18 mutation • PDGFR wild-type
    |
    imatinib
    9ms
    A mutation-based radiomics signature predicts response to imatinib in Gastrointestinal Stromal Tumors (GIST). (PubMed, Eur J Radiol Open)
    Indeed, with the latter setting 4 patients out of 5 were correctly predicted as non-responders. The results are a first step towards using radiomics to improve the management of patients with GIST, especially when tumor tissue is unavailable for molecular analysis or when molecular profiling is inconclusive.
    Journal • Stroma
    |
    KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    PDGFRA D842V • PDGFRA mutation • PDGFRA exon 18 mutation
    |
    imatinib
    10ms
    Testing the Use of Nilotinib and Paclitaxel as a Treatment for Patients With Prior Taxane Treatment, A ComboMATCH Treatment Trial (clinicaltrials.gov)
    P2, N=40, Recruiting, National Cancer Institute (NCI) | Initiation date: Jun 2023 --> Sep 2023
    Trial initiation date
    |
    PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    PDGFRA D842V • KIT L576P • KIT K642E • KIT V559 • KIT V559A • KIT W557
    |
    paclitaxel • Tasigna (nilotinib)
    10ms
    Testing the Use of Nilotinib and Paclitaxel as a Treatment for Patients With Prior Taxane Treatment, A ComboMATCH Treatment Trial (clinicaltrials.gov)
    P2, N=40, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting | Initiation date: Dec 2022 --> Jun 2023
    Enrollment open • Trial initiation date
    |
    PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    PDGFRA D842V • KIT L576P • KIT K642E • KIT V559 • KIT V559A • KIT W557
    |
    paclitaxel • Tasigna (nilotinib)
    11ms
    Myosin light chain kinase inhibition potentiates the anti-tumor effects of avapritinib in PDGFRA D842V-mutant gastrointestinal stromal tumor. (PubMed, Clin Cancer Res)
    MYLK upregulation is a novel mechanism of tumor persistence after tyrosine kinase inhibition. Concomitant MYLK inhibition may enable the use of a lower dose of avapritinib, which is associated with dose-dependent cognitive side effects.
    Journal • Stroma
    |
    PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • MYLK (Myosin Light Chain Kinase)
    |
    PDGFRA D842V • PDGFRA mutation
    |
    imatinib • Ayvakit (avapritinib)
    11ms
    Imatinib TDM in GIST (clinicaltrials.gov)
    P2, N=28, Not yet recruiting, Reema A. Patel | Initiation date: Apr 2023 --> Aug 2023
    Trial initiation date • Stroma
    |
    KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    KIT mutation • PDGFRA D842V • PDGFRA mutation
    |
    imatinib
    12ms
    Fluorine-18 fluorodeoxyglucose (18FDG)-uptake assessment of PDGFRA mutant gastrointestinal stromal tumors (GIST): A retrospective multicenter Italian study. (ASCO 2023)
    Background: D842V PDGFRA mutation identifies a molecular subtype of GIST, primarly resistant to imatinib and characterized by higher indolent behavior and a prominent immune profile... PDGFRA D842V-mutant GIST present an overall lower 18FDG uptake compared to other GIST subgroups. This feature could be related to their specific molecular background and is consistent with their higher tendency to an indolent behavior. Therefore, the role of functional imaging with 18FDG-PET in this subset of GIST is limited.
    Retrospective data • Stroma
    |
    KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    PDGFRA D842V • PDGFRA mutation
    |
    imatinib
    1year
    Long-term response to pimitespib in postoperative recurrent gastrointestinal stromal tumors with PDGFRA D842V mutation: a case report. (PubMed, Surg Case Rep)
    We report the first case of long-term response to PIMI in PDGFRA D842V mutant GIST. Pimitespib may be effective for treating GIST harboring this mutation by inhibiting HSP90.
    Journal • Stroma
    |
    PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)
    |
    PDGFRA D842V • PDGFRA mutation
    |
    imatinib • Ayvakit (avapritinib) • Jeselhy (pimitespib)
    1year
    AZURE: Study of Elenestinib (BLU-263) in Advanced Systemic Mastocytosis (AdvSM) and and Other KIT Altered Hematologic Malignancies (clinicaltrials.gov)
    P1/2, N=67, Recruiting, Blueprint Medicines Corporation | Not yet recruiting --> Recruiting
    Enrollment open • Combination therapy • Metastases
    |
    PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    KIT mutation • PDGFRA D842V • PDGFRA mutation • KIT D816V • KIT exon 17 mutation • PDGFRA fusion
    |
    azacitidine • elenestinib (BLU-263)
    1year
    AZURE: Study of Elenestinib (BLU-263) in Advanced Systemic Mastocytosis (AdvSM) and and Other KIT Altered Hematologic Malignancies (clinicaltrials.gov)
    P1/2, N=67, Not yet recruiting, Blueprint Medicines Corporation | N=108 --> 67 | Trial completion date: Nov 2027 --> Nov 2029 | Initiation date: Dec 2022 --> Apr 2023 | Trial primary completion date: Nov 2027 --> Nov 2029
    Enrollment change • Trial completion date • Trial initiation date • Trial primary completion date • Combination therapy • Metastases
    |
    PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    KIT mutation • PDGFRA D842V • PDGFRA mutation • KIT D816V • KIT exon 17 mutation • PDGFRA fusion
    |
    azacitidine • elenestinib (BLU-263)
    1year
    Imatinib TDM in GIST (clinicaltrials.gov)
    P2, N=28, Not yet recruiting, Reema A. Patel | Initiation date: Jan 2023 --> Apr 2023
    Trial initiation date • Stroma
    |
    KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    KIT mutation • PDGFRA D842V • PDGFRA mutation
    |
    imatinib
    1year
    Extragastrointestinal stromal tumour of the transverse mesocolon mimicking giant ovarian cystic neoplasm. (PubMed, BMJ Case Rep)
    This serves as an important lesson to keep the differential diagnosis broad when dealing with large cystic abdominal masses. The tumour was found to be KIT wild type, with a platelet-derived growth factor receptor alpha D842V mutation identified, conferring intrinsic resistance to imatinib.
    Journal • Stroma
    |
    PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    PDGFRA D842V • PDGFRA mutation • KIT wild-type
    |
    imatinib
    over1year
    Efficacy and Safety of Avapritinib in Treating Unresectable or Metastatic Gastrointestinal Stromal Tumors: A Phase I/II, Open-Label, Multicenter Study. (PubMed, Oncologist)
    Avapritinib was generally well tolerated and showed marked anti-tumor activity in Chinese patients with GIST bearing PDGFRA D842V mutations and notable efficacy as fourth- or later-line monotherapy (ClinicalTrials.gov Identifier: NCT04254939).
    Clinical • P1/2 data • Journal
    |
    PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    PDGFRA D842V • PDGFRA mutation
    |
    Ayvakit (avapritinib)
    over1year
    Clinicopathological and therapeutic analysis of PDGFRA mutated gastrointestinal stromal tumor. (PubMed, Pathol Res Pract)
    PDGFRA-mutant GIST mostly derived from stomach, with a relative indolent behavior. D842V mutation and lose of CD34 expression were adverse prognostic factors. Avapritinib can effectively control advanced patients in a certain period of time.
    Retrospective data • Journal
    |
    PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • CD34 (CD34 molecule)
    |
    PDGFRA D842V • PDGFRA mutation
    |
    Ayvakit (avapritinib)
    over1year
    miRNA Expression May Have Implications for Immunotherapy in PDGFRA Mutant GISTs. (PubMed, Int J Mol Sci)
    The miRNA-mRNA networks highlighted a signature of miRNAs/mRNA that could explain the indolent behavior of the D842V mutated GIST. The results highlighted a different miRNA fingerprint in PDGFRA D842V GISTs compared to non-D842Vmutated patients, which could explain the different biological behavior of this GIST subset.
    Journal • IO biomarker
    |
    PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    PDGFRA D842V • PDGFRA mutation • PDGFRA exon 18 mutation
    over1year
    Co-Localization of Gastrointestinal Stromal Tumors (GIST) and Peritoneal Mesothelioma: A Case Series. (PubMed, Ann Surg Oncol)
    One in 17 GIST patients undergoing resection in this series have PM, which is significantly higher than expected if these two diseases were considered as independent events. Our results indicate that synchronous co-occurrence of GIST and PM is an underrecognized finding, suggesting a possible relationship that deserves further investigation.
    Retrospective data • Journal
    |
    PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1)
    |
    PBRM1 mutation • BAP1 mutation • KIT exon 11 mutation • PDGFRA D842V • PDGFRA mutation
    over1year
    Advanced GIST: Which treatments in 2022 (PubMed, Bull Cancer)
    In advanced GIST, treatment is based on tyrosine kinase inhibitors, including imatinib, which has been the standard first-line treatment since the early 2000s, with sunitinib and regorafenib as second- and third-line standards, respectively...Ripretinib has become the validated fourth-line therapy for patients with KIT or PDGFRA non-D842V mutations, and avapritinib has been shown to be effective in patients with D842V mutations who were previously resistant to validated treatments...Specific treatments are available or under evaluation for some rare subgroups, and new therapeutic strategies are likely to further improve the management of advanced GIST in the coming years. This overview summarizes the results of recent trials and the place of these new molecules, as well as the main strategies under development for advanced GIST.
    Review • Journal
    |
    BRAF (B-raf proto-oncogene) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    KIT mutation • PDGFRA D842V • PDGFRA mutation
    |
    imatinib • Sutent (sunitinib) • Stivarga (regorafenib) • Ayvakit (avapritinib) • Qinlock (ripretinib)
    over1year
    Gastrointestinal stromal tumors (GIST) (PubMed, Wien Med Wochenschr)
    In cases of progressive disease after successive treatment with imatinib, sunitinib, and regorafenib, a fourth-line therapy with ripretinib was recently approved. Approved in 2020, avapritinib is the first effective targeted therapy for advanced stage GIST harboring an imatinib-resistant PDGFRA D842V mutation.
    Journal
    |
    KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    KIT mutation • PDGFRA D842V • PDGFRA mutation
    |
    imatinib • Sutent (sunitinib) • Stivarga (regorafenib) • Ayvakit (avapritinib) • Qinlock (ripretinib)
    over1year
    USING IN VITRO MODELS TO PREDICT IMATINIB RESPONSES IN PDGFRA-MUTANT GASTROINTESTINAL STROMAL TUMOR (CTOS 2022)
    Based on our data, over half of the unique and complex mutations observed in our PDGFRA-mutant GIST patient cohort would be predicted to be imatinib sensitive. Our predictive model has the potential to identify which patients with PDGFRA exon 18 mutant-GIST would benefit from front-line imatinib therapy as an alternative to avapritinib. Conversely, we could also identify those patients who would require treatment with front-line avapritinib.
    Preclinical
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    KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    KIT mutation • PDGFRA D842V • PDGFRA mutation • PDGFRA exon 18 mutation
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    imatinib • Sutent (sunitinib) • Stivarga (regorafenib) • Ayvakit (avapritinib) • Qinlock (ripretinib)
    over1year
    Imatinib TDM in GIST (clinicaltrials.gov)
    P2, N=28, Not yet recruiting, Reema A. Patel
    New P2 trial
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    KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    KIT mutation • PDGFRA D842V • PDGFRA mutation
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    imatinib
    almost2years
    DICER1-Associated Anaplastic Sarcoma of the Kidney With Coexisting Activating PDGFRA D842V Mutations and Response to Targeted Kinase Inhibitors in One Patient. (PubMed, JCO Precis Oncol)
    No abstract available
    Journal
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    PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • DICER1 (Dicer 1 Ribonuclease III)
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    PDGFRA D842V • PDGFRA mutation
    almost2years
    Clinicopathologic Characteristics and Prognosis of PDGFRA-Mutant Gastrointestinal Stromal Tumors: A Large-Scale, Multi-Institutional, Observational Study in China. (PubMed, Adv Ther)
    PDGFRA-mutant GIST mostly originated in the stomach and had a favorable prognosis after surgery. Non-D842V-mutant patients might have better prognoses than D842V-mutant patients. The prognostic model demonstrated favorable prediction accuracy, suggesting its clinical utility.
    Observational data • Retrospective data • Journal
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    PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
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    PDGFRA D842V • PDGFRA mutation
    almost2years
    New-Onset Parkinsonism in a Patient With Metastatic Gastrointestinal Stromal Tumor Treated With Avapritinib (APA 2022)
    He was started on olanzapine for these symptoms. An extensive work-up was negative for a paraneoplastic process, and the acute onset of rapidly progressing parkinsonian symptoms appears less consistent with a diagnosis of idiopathic Parkinson’s disease. Given the temporal relationship between the onset of symptoms coinciding with the initiation of avapritinib and the potential for neuropsychiatric side effects associated with avapritinib, we suspect that this drug contributed to a likely multifactorial etiology underlying this patient''s presentation and recommend clinicians be aware of the potential for this side effect.
    Clinical
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    KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    KIT mutation • PDGFRA D842V • PDGFRA mutation
    |
    Ayvakit (avapritinib) • olanzapine