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Table 1 Main clinical trials with targeted agents for ER+/HER2- advanced/metastatic breast cancer: mTOR inhibitors, PI3K inhibitors, and Akt inhibitors

From: Targeted therapies for ER+/HER2- metastatic breast cancer

Target Function Agent Trial Phase Design Results with significance/Study status
Line Arm CBR TTP Median PFS Median OS
mTOR mTOR inhibitor Evelorimus BOLERO-2 [1719] III nsAI failure EXE + evelorimus vs. EXE    10.6 mo vs. 4.1 mo n.s.
BOLERO-4 NCT01698918 II First line LET + evelorimus vs. LET Ongoing
BOLERO-6 NCT01783444 II nsAI failure EXE + evelorimus vs. EXE vs. capecitabine Ongoing
TAMRAD [20] II First line TAM + evelorimus vs. TAM 61 % vs. 42 % 8.5mo vs. 4.5mo   Not reached vs. 32.9mo
Tensirolimus HORIZON [21] III First line LET + tensirolimus vs. LET Terminated n.s.  
mTORC mTORC dual TORC1/2 inhibitor MLN0128 NCT02049957 I/II   MLN0128 + EXE vs. MLN0128 + FUL Ongoing
PI3K Pan-PI3 K inhibitor BKM120 BELLE-2 NCT01610284 III AI failure Fulvestrant + BKM120 vs. fulvestrant Ongoing
BELLE-3 NCT01633060 III mTOR inhibitor resisetance Fulvestrant + BKM120 vs. fulvestrant Ongoing
BELLE-4 NCT01572727 III First line BKM120 vs. BKM120 + PTX Terminated n.s.  
PI3K-α inhibitor BYL719 NCT02058381 II Premenopausal patients BYL719 + TAM + Gos vs. BKM120 + TAM + Gos vs. TAM + Gos Ongoing
Pan-PI3K inhibitor/dual PI3K/mTOR inhibitor XL147/XL765 NCT01082068 I/II nsAI failure XL147 + LET vs. XL765 + LET Completed
dual PI3K/mTOR inhibitor GDC0941/GDC0980 NCT01437566 II AI failure Fulvestrant + GDC0941 vs. fulvestrant + GDC0980 vs. fulvestrant ORR 7.9 % vs. unknown vs. 6.3 %   6.6mo vs. unknown vs. 5.1mo  
Akt Akt inhibitor AZD2014 MANTA NCT02216786 II AI failure AZD2014 + FUL vs. everolimus + FUL vs. FUL Ongoing
AZD5363 BEECH NCT01625286 I/II Part B: PI3CA mut AZD5363 + wPTX vs. wPTX Ongoing
MK2206 NCT01277757 II PIK3CA mut AKT mut PTEN loss/mut Monotherapy Terminated
  1. Abbreviations: mTOR: mammalian target of rapamycin, AI: aromatase inhibitor, nsAI: non-steroidal AI, EXE: exemestane, LET: letrozole, TAM: tamoxifen, TORC: mTOR complex, FUL: fulvestrant, PI3K: phosphatidylinositol-3-kinase, PTX: paclitaxel, Gos: goserelin, Akt: protein kinase B