Table 5.
Clinical trials of PAM inhibitors in triple negative breast cancer (TNBC).
| Target | Drug | Study (Phase) | Patient Population | Regimen and Outcome | Reference |
|---|---|---|---|---|---|
| Pan-PI3K | Buparlisib (BKM120) |
NCT01790932 (II) |
Metastatic TNBC | CBR:12% (6 patients, all SD ≥ 4 months) mPFS: 1.8 months (95% CI: 1.6–2.3) mOS: 11.2 months (95% CI: 6.2–25) |
[134] |
| AKT1-3 | Capivasertib | (II) | Metastatic TNBC | Capivasertib vs. Placebo + paclitaxel (mPFS: 5.9 vs. 4.2 months; p = 0.06) (mOS 19.1 vs. 12.6 months; p = 0.04) |
[135] |
| Pan-AKT | GDC-0068 (Ipatasertib) |
LOTU (II) |
Metastatic TNBC | Ipatasertib vs. placebo + paclitaxel (mPFS 6.2 vs. 4.9 months; HR: 0.60; p = 0.037) |
[136] |
| FAIRLANE (II) |
Early TNBC | Ipatasertib + paclitaxel vs. placebo + paclitaxel pCR rates: 17% vs. 13% |
[137] | ||
| LY2780301 | TAKTIC (Ib/II) |
HER2-ABC | 6-month ORR:63.9% [48.8–76.8] | [138] | |
| mTOR | Everolimus (DAE) |
NCT00930930 (II) |
II/III TNBC (Neoadjuvant therapy) |
Everolimus vs. placebo (5pCR: 36% vs. 49%) |
[139] |
| Temsirolimus (DAT) |
NCT00761644 (II) |
Metaplastic TNBC | Doxorubicin + bevacizumab + DAT or DAE ORR: 21%; CBR: 40% PI3K pathway alteration: ORR: (31% vs. 0%; p = 0.04); CBR (44% vs. 45%; p > 0.99). |
[140] | |
| PI3K-mTOR | Eganelisib |
NCT03719326 (I/Ib) |
Advanced or metastatic TNBC |
In combination with pegylated liposomal doxorubicin (PLD) or A2aR/A2bR antagonist-1(AB928) NA |
- |
CI, confident interval; SD, stable disease; mOS, median overall survival; mPFS, median Progression-Free Survival; pCR, pathological complete response; NA: not available.