Table 4 Selected clinical trials targeting intracellular signalling pathways in triple negative breast cancer
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 1Â month |
MDV3100-11 [148] | AR inhibitor (enzalutamide) | Enzalutamide | II | Advanced TNBC | 4-month clinical benefit rate 25% (95%CI 17%-33%) Median PFS 2.9Â 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 |