Clinical characteristics and treatment outcome in a large multicentre observational cohort of PDGFRA exon 18 mutated gastrointestinal stromal tumour patients

Sheima Farag, Neeta Somaiah, Haesun Choi, Birthe Heeres, Wei-Lien Wang, Hester van Boven, Petra Nederlof, Robert Benjamin, Winette van der Graaf, Dirk Grunhagen, Pieter Boonstra, Anna K.L. Reyners, Hans Gelderblom, Neeltje Steeghs

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Purpose Patients, platelet-derived growth factor receptor alpha (PDGFRA) D842V-mutated gastrointestinal stromal tumours (GISTs) are known for their insensitivity to imatinib. However, in clinical practice responses have been observed in some patients. We describe the natural history and treatment outcomes in a cohort of PDGFRA exon 18 mutated GIST patients. Patients and methods A retrospective cohort study was conducted in PDGFRA exon 18 mutation GIST patients treated in six expert centres in the Netherlands and the United States. Two independent radiologists assessed radiological response to imatinib according to Choi's criteria in all patients with measurable disease treated with imatinib in neo-adjuvant or palliative intent. Results Seventy-one patients with PDGFRA exon 18 mutation were identified of whom 48 patients (69%) had a D842V mutation. Twenty-two (45.8%) D842V-mutated GIST patients received imatinib treatment, 16 had measurable disease. Fourteen out of the 23 (60.9%) patients with non-D842V mutations received imatinib treatment, eight had measurable disease. Two out of 16 (12.5%) D842V-mutated GIST patients had partial response, 3 patients (18.8%) had stable disease and 9 patients (56.3%) had progressive disease as best response. Two patients did not have follow-up computed tomography scans to assess response. Six out of 8 (75%) patients with non-D842V exon 18 mutations had partial response and two (25%) had stable disease as best response. Conclusion Patients with D842V-mutated GISTs can occasionally respond to imatinib. In the absence of better therapeutic options, imatinib should therefore not be universally withheld in patients with this mutation.

Original languageEnglish (US)
Pages (from-to)76-83
Number of pages8
JournalEuropean Journal of Cancer
Volume76
DOIs
StatePublished - May 1 2017

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Platelet-Derived Growth Factor alpha Receptor
Exons
Gastrointestinal Stromal Tumors
Mutation

Keywords

  • D842V
  • GIST
  • Gastrointestinal stromal tumour
  • Imatinib
  • PDGFRA exon 18

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Clinical characteristics and treatment outcome in a large multicentre observational cohort of PDGFRA exon 18 mutated gastrointestinal stromal tumour patients. / Farag, Sheima; Somaiah, Neeta; Choi, Haesun; Heeres, Birthe; Wang, Wei-Lien; van Boven, Hester; Nederlof, Petra; Benjamin, Robert; van der Graaf, Winette; Grunhagen, Dirk; Boonstra, Pieter; Reyners, Anna K.L.; Gelderblom, Hans; Steeghs, Neeltje.

In: European Journal of Cancer, Vol. 76, 01.05.2017, p. 76-83.

Research output: Contribution to journalArticle

Farag, S, Somaiah, N, Choi, H, Heeres, B, Wang, W-L, van Boven, H, Nederlof, P, Benjamin, R, van der Graaf, W, Grunhagen, D, Boonstra, P, Reyners, AKL, Gelderblom, H & Steeghs, N 2017, 'Clinical characteristics and treatment outcome in a large multicentre observational cohort of PDGFRA exon 18 mutated gastrointestinal stromal tumour patients', European Journal of Cancer, vol. 76, pp. 76-83. https://doi.org/10.1016/j.ejca.2017.02.007
Farag, Sheima ; Somaiah, Neeta ; Choi, Haesun ; Heeres, Birthe ; Wang, Wei-Lien ; van Boven, Hester ; Nederlof, Petra ; Benjamin, Robert ; van der Graaf, Winette ; Grunhagen, Dirk ; Boonstra, Pieter ; Reyners, Anna K.L. ; Gelderblom, Hans ; Steeghs, Neeltje. / Clinical characteristics and treatment outcome in a large multicentre observational cohort of PDGFRA exon 18 mutated gastrointestinal stromal tumour patients. In: European Journal of Cancer. 2017 ; Vol. 76. pp. 76-83.
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title = "Clinical characteristics and treatment outcome in a large multicentre observational cohort of PDGFRA exon 18 mutated gastrointestinal stromal tumour patients",
abstract = "Purpose Patients, platelet-derived growth factor receptor alpha (PDGFRA) D842V-mutated gastrointestinal stromal tumours (GISTs) are known for their insensitivity to imatinib. However, in clinical practice responses have been observed in some patients. We describe the natural history and treatment outcomes in a cohort of PDGFRA exon 18 mutated GIST patients. Patients and methods A retrospective cohort study was conducted in PDGFRA exon 18 mutation GIST patients treated in six expert centres in the Netherlands and the United States. Two independent radiologists assessed radiological response to imatinib according to Choi's criteria in all patients with measurable disease treated with imatinib in neo-adjuvant or palliative intent. Results Seventy-one patients with PDGFRA exon 18 mutation were identified of whom 48 patients (69{\%}) had a D842V mutation. Twenty-two (45.8{\%}) D842V-mutated GIST patients received imatinib treatment, 16 had measurable disease. Fourteen out of the 23 (60.9{\%}) patients with non-D842V mutations received imatinib treatment, eight had measurable disease. Two out of 16 (12.5{\%}) D842V-mutated GIST patients had partial response, 3 patients (18.8{\%}) had stable disease and 9 patients (56.3{\%}) had progressive disease as best response. Two patients did not have follow-up computed tomography scans to assess response. Six out of 8 (75{\%}) patients with non-D842V exon 18 mutations had partial response and two (25{\%}) had stable disease as best response. Conclusion Patients with D842V-mutated GISTs can occasionally respond to imatinib. In the absence of better therapeutic options, imatinib should therefore not be universally withheld in patients with this mutation.",
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author = "Sheima Farag and Neeta Somaiah and Haesun Choi and Birthe Heeres and Wei-Lien Wang and {van Boven}, Hester and Petra Nederlof and Robert Benjamin and {van der Graaf}, Winette and Dirk Grunhagen and Pieter Boonstra and Reyners, {Anna K.L.} and Hans Gelderblom and Neeltje Steeghs",
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T1 - Clinical characteristics and treatment outcome in a large multicentre observational cohort of PDGFRA exon 18 mutated gastrointestinal stromal tumour patients

AU - Farag, Sheima

AU - Somaiah, Neeta

AU - Choi, Haesun

AU - Heeres, Birthe

AU - Wang, Wei-Lien

AU - van Boven, Hester

AU - Nederlof, Petra

AU - Benjamin, Robert

AU - van der Graaf, Winette

AU - Grunhagen, Dirk

AU - Boonstra, Pieter

AU - Reyners, Anna K.L.

AU - Gelderblom, Hans

AU - Steeghs, Neeltje

PY - 2017/5/1

Y1 - 2017/5/1

N2 - Purpose Patients, platelet-derived growth factor receptor alpha (PDGFRA) D842V-mutated gastrointestinal stromal tumours (GISTs) are known for their insensitivity to imatinib. However, in clinical practice responses have been observed in some patients. We describe the natural history and treatment outcomes in a cohort of PDGFRA exon 18 mutated GIST patients. Patients and methods A retrospective cohort study was conducted in PDGFRA exon 18 mutation GIST patients treated in six expert centres in the Netherlands and the United States. Two independent radiologists assessed radiological response to imatinib according to Choi's criteria in all patients with measurable disease treated with imatinib in neo-adjuvant or palliative intent. Results Seventy-one patients with PDGFRA exon 18 mutation were identified of whom 48 patients (69%) had a D842V mutation. Twenty-two (45.8%) D842V-mutated GIST patients received imatinib treatment, 16 had measurable disease. Fourteen out of the 23 (60.9%) patients with non-D842V mutations received imatinib treatment, eight had measurable disease. Two out of 16 (12.5%) D842V-mutated GIST patients had partial response, 3 patients (18.8%) had stable disease and 9 patients (56.3%) had progressive disease as best response. Two patients did not have follow-up computed tomography scans to assess response. Six out of 8 (75%) patients with non-D842V exon 18 mutations had partial response and two (25%) had stable disease as best response. Conclusion Patients with D842V-mutated GISTs can occasionally respond to imatinib. In the absence of better therapeutic options, imatinib should therefore not be universally withheld in patients with this mutation.

AB - Purpose Patients, platelet-derived growth factor receptor alpha (PDGFRA) D842V-mutated gastrointestinal stromal tumours (GISTs) are known for their insensitivity to imatinib. However, in clinical practice responses have been observed in some patients. We describe the natural history and treatment outcomes in a cohort of PDGFRA exon 18 mutated GIST patients. Patients and methods A retrospective cohort study was conducted in PDGFRA exon 18 mutation GIST patients treated in six expert centres in the Netherlands and the United States. Two independent radiologists assessed radiological response to imatinib according to Choi's criteria in all patients with measurable disease treated with imatinib in neo-adjuvant or palliative intent. Results Seventy-one patients with PDGFRA exon 18 mutation were identified of whom 48 patients (69%) had a D842V mutation. Twenty-two (45.8%) D842V-mutated GIST patients received imatinib treatment, 16 had measurable disease. Fourteen out of the 23 (60.9%) patients with non-D842V mutations received imatinib treatment, eight had measurable disease. Two out of 16 (12.5%) D842V-mutated GIST patients had partial response, 3 patients (18.8%) had stable disease and 9 patients (56.3%) had progressive disease as best response. Two patients did not have follow-up computed tomography scans to assess response. Six out of 8 (75%) patients with non-D842V exon 18 mutations had partial response and two (25%) had stable disease as best response. Conclusion Patients with D842V-mutated GISTs can occasionally respond to imatinib. In the absence of better therapeutic options, imatinib should therefore not be universally withheld in patients with this mutation.

KW - D842V

KW - GIST

KW - Gastrointestinal stromal tumour

KW - Imatinib

KW - PDGFRA exon 18

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