Olaratumab had an acceptable safety profile and may improve disease control in patients with PDGFRα mutation-positive gastrointestinal stromal tumor (GIST), according to a study published in Annals of Oncology.1

This open-label, phase 2 study (ClinicalTrials.gov Identifier: NCT01316263) enrolled 30 previously treated patients with unresectable and/or metastatic GIST regardless of PDGFRα mutation status. All PDGFRα mutations were D842V mutations. Participants received olaratumab 20 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity.

Results showed that none of the evaluable 20 patients achieved a complete response or a partial response; however, 50.0% of the 6 patients with PDGFRα mutation-positive disease and 14.3% of the 14 patients without a PDGFRα mutation had stable disease. The rest experienced progressive disease.

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Among patients with PDGFRα mutation-positive GIST, the 12-week clinical benefit rate was 50.0% (90% CI, 15.3-84.7) vs 14.3% (90% CI, 2.6-38.5) in those without a PDGFRα mutation; median progression-free survival was 32.1 weeks (90% CI, 5.0-35.9) and 6.1 weeks (90% CI, 5.7-6.3), respectively.

Median overall survival was not reached in the PDGFRα mutation-positive cohort and was 24.9 weeks (90% CI, 14.4-49.1) in the group without a PDGFRα mutation.

The most common treatment-related adverse events were fatigue, nausea, and peripheral edema. One patients with a PDGFRα mutation experienced grade 3 or higher syncope and 1 without a PDGFRα mutation had grade 3 or worse hypertension.

The findings ultimately suggest that patients with PDGFRα-mutant advanced GIST may derive clinical benefit from treatment with olaratumab. Further investigation with a larger sample size is necessary to confirm these results.

RELATED: Imatinib and GISTs: Genomic Subtypes and Survival Outcomes

Olaratumab is a PDGFRα-blocking antibody approved by the U.S. Food and Drug Administration in combination with doxorubicin for the treatment of adult patients with soft tissue sarcoma with a histologic subtype for which an anthracycline-containing regimen is appropriate and which is not amenable to curative treatment with radiotherapy or surgery.


  1. Wagner AJ, Kindler H, Gelderblom H, et al. A phase II study of a human anti-PDGFRα monoclonal antibody (olaratumab, IMC-3G3) in previously treated patients with unresectable and/or metastatic gastrointestinal stromal tumors. Ann Oncol. 2017 Feb 13. doi: 10.1093/annonc/mdw659 [Epub ahead of print]