BREAST CANCER: Real-world data from the GENIE consortium suggest a benefit for MTOR inhibition where tumours harbour an AKT E17K mutation.

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April 14, 2020

SCIENTIFIC

BREAST CANCER:  Real-world data from the GENIE consortium suggest a benefit for MTOR inhibition where tumours harbour an AKT E17K mutation.

Characteristics and outcome of AKT1 E17K-mutant breast cancer defined through AACR GENIE, a clinicogenomic registry

Lillian M Smyth et al

Cancer Discovery: January 10, 2020 doi: 10.1158/2159-8290.CD-19-1209

Abstract

AKT inhibitors have promising activity in AKT1 E17K-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 matched AKT1 E17K-mutant (n=153) and -wildtype (n=302) metastatic breast cancer patients.

AKT1-mutant cases had similar adjusted overall survival (OS) compared with AKT1-wildtype 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.