Table 2.
Clinical trials of PI3K inhibitors in ER+/HER2− breast cancer.
| Target | Drug | Study (Phase) | Patient Population | Regimen and Outcome | FDA/EMA Approval | Reference |
|---|---|---|---|---|---|---|
| Pan-PI3K | Buparisib (BKMI20) |
BELLE-2 (III) |
HR (+), HER2 (−), ABC/MBC (second line) |
buparlisib + fulvestrant vs. placebo + fulvestrant (mPFS: 6.9 vs. 5.0 months; HR: 0.78; p = 0.00021) |
N | [78] |
| BELLE-3 (II) |
HR (+), HER2 (−), ABC/MBC relapsed on or after endocrine therapy and mTOR inhibitors | buparlisib vs. Placebo (mPFS: 3.9 vs. 1.8 months; HR: 0.67; p = 0.0003) |
[79] | |||
| Pictilisib (GDC-0941) |
FERGI (II) |
HR (+), HER2 (−), ABC/MBC Al-resistant |
pictilisib + fulvestrant vs. placebo + fulvestrant (mPFS:6.6 vs. 5.1 months; HR: 0.74; p = 0.096) |
N | [80] | |
| PEGGY (II) |
HR (+), HER2 (−) metastatic breast cancer |
Pictilisib + paclitaxel vs. placebo + paclitaxel (mPFS:8.2 vs. 7.8 months; HR: 0.95) | [81] | |||
| PI3K (p110α) |
Alpelisib (BYL719) |
SOLAR-1 (III) |
HR (+), HER2 (−), ABC Received endocrine therapy previously |
PIK3CA-mutated: alpelisib vs. placebo (mPFS 11.0 vs. 5.7 months; HR: 0.65; p < 0.001); (mOS: 39.3 vs. 31.4 months; HR: 0.86; p = 0.15) |
Y | [82] |
| BYLieve (II) |
HR (+), HER2 (−), PIK3CA-mutant ABC progressed on/after prior therapy, including CDK inhibitors |
proportion of without disease progression at 6 month was 50.4% (95% CI: 41.2–59.6). | [83] | |||
| NEO-ORB (II) |
HR (+), HER2 (−) Postmenopausal women Tlc-T3 breast cancer |
Alpelisib + letrozole vs. placebo + letrozde, ORR: 43% vs. 45%, PIK3CA-wild-type vs. mutant ORR: 63% vs. 61% |
[84] | |||
| Taselisib (GDC0032) |
SANDPIPER (III) |
Postmenopausal women, disease recurrence/progression during/after AI |
Taselisib vs. placebo (PFS: 7.4 vs. 5.4 months; HR: 0.70: p = 0.0037) |
N | [85] | |
| PI3K-mTOR | Gedatolisib |
NCT02684032 (I) |
metastatic breast cancer | NA | N | [86] |
| Apitolisib |
NCT01254526 (Ib) |
locally recurrent breast cancer or metastatic breast cancer |
NA | N | [87] | |
| Samotolisib |
NCT02057133 (I) |
In combination with: letrozole, anastrozole, tamoxifen, exemestane | NA | N | [88] |
Al, aromatase inhibitor; mPFS, median progression-free survival; HR, hazard ratio: MBC, metastatic breast cancer. ABC, advanced breast cancer; ORR, objective response rate; NA, not applicable or discontinued owing to drug toxicity; EMA, European Medicines Agency; N, not yet approved; Y, approved. FDA, Food and Drug Administration.