Avapritinib: novel hope for patients with metastatic gist with PDGFRA exon 18 mutation

Authors

  • Sachin Maggo Department of Medicine, Army Hospital, Joshimath, Uttarakhand, India
  • A. P. Dubey Department of Oncology, Santhosh Medical College, Ghaziabad, Uttar Pradesh, India
  • Pawan Dhull Department of Neurology, Command Hospital, Lucknow, Uttar Pradesh, India
  • Nilabh Kumar Singh Department of Medicine, Army Hospital, Tejpur, Assam, India

DOI:

https://doi.org/10.18203/2319-2003.ijbcp20202960

Keywords:

Avapritinib, Metastatic GIST, PDGFRA mutation, Tyrosine kinase inhibitors

Abstract

Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms of the gastrointestinal tract associated with high rates of malignant transformation. The activating mutations in platelet-derived growth factor receptor A (PDGFRA) have been linked to the development of GISTs, and up to approximately 10% of GIST cases involve mutations of this gene. Current treatment options for metastatic GIST are minimal, mainly trusting on tyrosine kinase inhibitors (TKIs) such as Imatinib, Sunitinib and Regorafenib. However, eventually, most patients develop resistance to TKIs, usually due to the acquisition of secondary mutations. Moreover, 5-6% of patients with unresectable of metastatic GIST have the primary PDGFRA D842V mutation, which makes it resistant to all approved treatment options. Avapritinib, a potent and selective TKI of KIT and PDGFRA activation loop mutants. The drug demonstrates anti-tumor activity by inhibiting the autophosphorylation of KIT D816V and PDGFRA D842V, thereby terminating the downstream signalling. The drug is available in oral formulation with a recommended dosage of 300 mg once daily. The onset of Avapritinib is fast, shows rapid absorption and linear pharmacokinetics. Most common adverse reactions seen are edema, fatigue, abdominal pain, and neurocognitive defects. Clinical trials for Avapritinib have been positive, and results suggest that the drug may be a new safe and effective option for metastatic GIST treatment. With Blueprint Medicines having already received US FDA approval in January 2020, Avapritinib may soon be an addition to the mounting armoury of drugs against metastatic GIST harbouring PDGFRA exon 18 mutation.

Author Biographies

Sachin Maggo, Department of Medicine, Army Hospital, Joshimath, Uttarakhand, India

Dr Sachin Maggo

MD Internal Medicine

Department of Medicine

A. P. Dubey, Department of Oncology, Santhosh Medical College, Ghaziabad, Uttar Pradesh, India

Dr A P Dubey
DNB (Medical Oncology)

Department of Oncology

Pawan Dhull, Department of Neurology, Command Hospital, Lucknow, Uttar Pradesh, India

Dr Pawan Dhull

DNB (Neurology)

Professor

Nilabh Kumar Singh, Department of Medicine, Army Hospital, Tejpur, Assam, India

Dr Nilabh Kumar Singh

MD, Internal Medicine

Department of Medicine

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Published

2020-06-26

How to Cite

Maggo, S., Dubey, A. P., Dhull, P., & Singh, N. K. (2020). Avapritinib: novel hope for patients with metastatic gist with PDGFRA exon 18 mutation. International Journal of Basic & Clinical Pharmacology, 9(7), 1175–1179. https://doi.org/10.18203/2319-2003.ijbcp20202960

Issue

Section

New Drug Update