Clinical characteristics and treatment outcome in a large multicentre observational cohort of PDGFRA exon 18 mutated gastrointestinal stromal tumour patients.
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Date
2017-05ICR Author
Author
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, PA
Reyners, AKL
Gelderblom, H
Steeghs, N
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Humans
Esophageal Neoplasms
Stomach Neoplasms
Gastrointestinal Stromal Tumors
Receptor, Platelet-Derived Growth Factor alpha
Antineoplastic Agents
Prognosis
Treatment Outcome
Chemotherapy, Adjuvant
Neoadjuvant Therapy
Palliative Care
Digestive System Surgical Procedures
Retrospective Studies
Cohort Studies
Mutation
Adult
Aged
Aged, 80 and over
Middle Aged
United States
Netherlands
Female
Male
Young Adult
Imatinib Mesylate
Research team
Clinical and Translational Sarcoma
Language
eng
Date accepted
2017-02-05
License start date
2017-05
Citation
European journal of cancer (Oxford, England : 1990), 2017, 76 pp. 76 - 83