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Table 4 Selected clinical trials targeting intracellular signalling pathways in triple negative breast cancer

From: Heterogeneity of triple negative breast cancer: Current advances in subtyping and treatment implications

Trial Target Treatment vs. control arm Phase Setting Key results
(Treatment vs. control)
Strategies targeting the PI3K/AKT pathway
LOTUS [142] AKT inhibitor
(ipatasertib)
Ipatasertib + paclitaxel
vs
Placebo + paclitaxel
II Advanced TNBC ITT population
PFS 6.2 months vs. 4.9 months
HR 0.60 (95%CI 0.37–0.98; P = 0.037)
PI3K/AKT/PTEN altered population PFS 9 months vs. 4.9 months
HR 0.44 (95%CI 0.20–0.99; P = 0.04)
PAKT [143] AKT inhibitor
(capivasertib)
Capivasertib + paclitaxel
vs
Placebo + paclitaxel
II Advanced TNBC ITT population PFS 5.9 months vs. 4.2 months
HR 0.74 (95%CI 0.50–1.08; P = 0.11)
PI3K/AKT/PTEN altered population PFS 9.3 months vs. 3.7 months
HR 0.30 (95%CI 0.11–0.79; P = 0.01)
IPATunity
130 [144]
AKT inhibitor
(ipatasertib)
Ipatasertib + paclitaxel
vs
Placebo + paclitaxel
III Advanced TNBC with PI3K/AKT/PTEN alterations PFS 7.4 months vs. 6.1 months
HR 1.02 (95%CI 0.71–1.45)
CAPItello 290 [145] AKT inhibitor
(capivasertib)
capivasertib + paclitaxel
vs
Placebo + paclitaxel
III Advanced TNBC Ongoing
Primary endpoint is PFS
Secondary endpoints include OS
Strategies targeting androgen receptor signalling
TBCRC011 [147] AR inhibitor
(bicalutamide)
Bicalutamide II Advanced ER/PR negative breast cancer 6-month clinical benefit rate 19% (95%CI 7%-39%)
Median PFS 1 month
MDV3100-11 [148] AR inhibitor
(enzalutamide)
Enzalutamide II Advanced TNBC 4-month clinical benefit rate 25% (95%CI 17%-33%)
Median PFS 2.9 months
TBCRC032 [149] AR inhibitor
(enzalutamide)
 + 
PI3K inhibitor
(taselisib)
Enzalutamide
 + taselisib
vs
enzalutamide alone
IB + II Advanced TNBC
with AR ≥ 10% by IHC
Evaluable patients on combination 4-month clinical benefit rate 35.7% while no clinical benefit on enzalutamide only
Luminal androgen receptor TNBC subtype population
4-month clinical benefit rate (75% vs. 12.5%; P = 0.06) and (median PFS 4.6 months vs. 2 months; P = 0.08) compared to other TNBC subtypes
  1. Abbreviations: ITT intention-to-treat, PFS progression free survival, OS overall survival, HR hazard ratio, CI confidence interval, AR androgen receptor, IHC immunohistochemistry, TNBC triple negative breast cancer