Abstract:
:AKT inhibitors have promising activity in AKT1E17K-mutant estrogen receptor (ER)-positive metastatic breast cancer, but the natural history of this rare genomic subtype remains unknown. Utilizing AACR Project GENIE, an international clinicogenomic data-sharing consortium, we conducted a comparative analysis of clinical outcomes of patients with matched AKT1E17K-mutant (n = 153) and AKT1-wild-type (n = 302) metastatic breast cancer. AKT1-mutant cases had similar adjusted overall survival (OS) compared with AKT1-wild-type controls (median OS, 24.1 vs. 29.9, respectively; P = 0.98). AKT1-mutant cases enjoyed longer durations on mTOR inhibitor therapy, an observation previously unrecognized in pivotal clinical trials due to the rarity of this alteration. Other baseline clinicopathologic features, as well as durations on other classes of therapy, were broadly similar. In summary, we demonstrate the feasibility of using a novel and publicly accessible clincogenomic registry to define outcomes in a rare genomically defined cancer subtype, an approach with broad applicability to precision oncology. SIGNIFICANCE: We delineate the natural history of a rare genomically distinct cancer, AKT1E17K-mutant ER-positive breast cancer, using a publicly accessible registry of real-world patient data, thereby illustrating the potential to inform drug registration through synthetic control data.See related commentary by Castellanos and Baxi, p. 490.
journal_name
Cancer Discovjournal_title
Cancer discoveryauthors
Smyth LM,Zhou Q,Nguyen B,Yu C,Lepisto EM,Arnedos M,Hasset MJ,Lenoue-Newton ML,Blauvelt N,Dogan S,Micheel CM,Wathoo C,Horlings H,Hudecek J,Gross BE,Kundra R,Sweeney SM,Gao J,Schultz N,Zarski A,Gardos SM,Lee J,Sdoi
10.1158/2159-8290.CD-19-1209subject
Has Abstractpub_date
2020-04-01 00:00:00pages
526-535issue
4eissn
2159-8274issn
2159-8290pii
2159-8290.CD-19-1209journal_volume
10pub_type
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