Background: Activating mutations in KIT or PDGFRA kinases drive the vast majority of GIST in adult pts, making the disease highly amenable to targeted therapy. KIT-driven disease is more common (~80% of cases of advanced GIST), while PDGFRA-driven GIST is rare (~5-10% of cases of advanced GIST). TKIs have transformed therapy of advanced GIST; however, evidence suggests the benefit of currently approved TKIs has been predominantly in patients with KIT-driven GIST. We initiated this study to characterize response and survival of pts with PDGFRα D842 mutant GIST treated with currently approved TKIs. Methods: This was a multicenter, retrospective study of adult pts with locally advanced, metastatic, or recurrent PDGFRα D842 mutant GIST diagnosed between Jan 2000 and Jul 2016 who were treated with at least one TKI. Demographic and clinical data were collected through chart review and analyzed to determine overall survival (OS) and best overall response, duration of response, and progression-free survival (PFS) for each line of TKI therapy. Results: Twenty-two pts, all with PDGFRα D842V GIST, were identified at 3 US academic institutions: men, n = 15; median age, 57 y [range: 31-72]; median TKI lines of therapy, 4 [range: 1–8]. Ten pts had primary tumor size ≥ 15 cm, and 8 pts had mitotic index > 10/50 HPF at the time of diagnosis. Imatinib was the most common TKI used (n = 21); followed by sunitinib (n = 15), dasatinib (n = 8), sorafenib (n = 6), regorafenib (n = 4), nilotinib (n = 2) and pazopanib (n = 1). Imatinib was the first line TKI in 20 pts (91%). Only 1 (5%) pt responded to first-line TKI therapy (complete response to imatinib in a pt with residual disease following primary resection). Median PFS on first line TKI was 6.4 months. Median OS from initial diagnosis of GIST was 4.2 years. Conclusions: These results confirm and extend previous data suggesting that pts with advanced PDGFRα D842V GIST have a low response rate, and poor overall survival with currently available TKIs. To transform therapy for PDGFRa D842V GIST, novel TKIs that potently and selectively inhibit D842V mutant PDGFRα are needed.