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Title
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A phase II study of a human anti-PDGFR alpha monoclonal antibody (olaratumab, IMC-3G3) in previously treated patients with metastatic gastrointestinal stromal tumors
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Author
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Abstract
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| Background: This study evaluated tumor response to olaratumab (an anti-PDGFR alpha monoclonal antibody) in previously treated patients with metastatic gastrointestinal stromal tumor (GIST) with or without PDGFR alpha mutations (cohorts 1 and 2, respectively). Patients and methods: Patients received olaratumab 20 mg/kg intravenously every 14 days until disease progression, death, or intolerable toxicity occurred. Outcome measures were 12-week tumor response, progression-free survival (PFS), overall survival (OS), and safety. Results: Of 30 patients enrolled, 21 patients received >= 1 dose of olaratumab. In the evaluable population (cohort 1, n = 6; cohort 2, n = 14), no complete response (CR) or partial response (PR) was observed. Stable disease (SD) was observed in 3 patients (50.0%) in cohort 1 and 2 patients (14.3%) in cohort 2. Progressive disease (PD) was observed in 3 patients (50.0%) in cohort 1 and 12 patients (85.7%) in cohort 2. The 12-week clinical benefit rate (CR+PR+SD) (90% CI) was 50.0% (15.3-84.7%) in cohort 1 and 14.3% (2.6-38.5%) in cohort 2. SD lasted beyond 12 weeks in 5 patients (cohort 1, n = 3; cohort 2, n = 2). Median PFS (90% CI) was 32.1 (5.0-35.9) weeks in cohort 1 and 6.1 (5.7-6.3) weeks in cohort 2. Median OS was not reached in cohort 1 and was 24.9 (14.4-49.1) weeks in cohort 2. All patients in cohort 1 and 9 (64.3%) in cohort 2 experienced an olaratumab-related adverse event (AE), most commonly fatigue (38.1%), nausea (19.0%), and peripheral edema (14.3%). Two grade >= 3 olaratumab-related events were reported (cohort 1, syncope; cohort 2, hypertension). Conclusions: Olaratumab had an acceptable AE profile in patients with GIST. While there was no apparent effect on PFS in patients without PDGFR alpha mutations, patients with PDGFR alpha-mutant GIST (all with D842V mutations) treated with olaratumab had longer disease control compared with historical data for this genotype. |
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Language
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English
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Source (journal)
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Annals of oncology / European Society for Medical Oncology. - Amsterdam
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Publication
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Amsterdam
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2017
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ISSN
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0923-7534
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DOI
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10.1093/ANNONC/MDW659
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Volume/pages
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28
:3
(2017)
, p. 541-546
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ISI
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000397300100018
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Pubmed ID
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28426120
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Full text (Publisher's DOI)
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Full text (open access)
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