Table 1.
Pivotal trials on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway.
| Author, Year [Ref] |
Trial | Study Design | N° Patients | Treatment Line | Drug | Primary Endpoints | Results |
|---|---|---|---|---|---|---|---|
| Bachelot, 2012 [23] |
TAMRAD | Phase II Randomized 1:1 | 111 | Progressed on previous ET | EVE plus TAM versus TAM |
CBR | 61.1% versus 42.1% |
| Yardley, 2013 [22] |
BOLERO-2 | Phase III Placebo-controlled Double-blind Randomized 2:1 |
724 | Progressed on previous ET | EVE plus EXE versus PBO plus EXE |
PFS | 11.0 versus 4.1 mo, p < 0.0001 |
| Baselga, 2017 [40] |
BELLE-2 | Phase III Placebo-controlled Double-blind Randomized 1:1 |
1147 | Progressed on previous ET | BUP plus F500 versus PBO plus F500 |
PFS (overall population and inactivated or non-activated PI3K pathway) |
Overall population (n = 1147) 6.9 versus 5.0 mo, p = 0.00021; PIK3CA mutant (n = 200) 7.0 versus 3.2 mo, p = 0.0005 PIK3CA WT (n = 387) 6.8 versus 6.8 mo, p = 0.642 PI3K activated (n = 372) 6.8 versus 4.0 mo, p = 0.014 PI3K non-activated (n = 479) NR |
| Krop, 2016 [42] |
FERGI | Phase II Placebo-controlled Double-blind Randomized: 1:1 (part 1) 2:1 (part 2) |
168 (part 1) 61 (part 2) |
Progressed on previous ET | PIC plus F500 versus PBO plus F500 |
PFS (overall population and in patients with PI3K mutated tumors) |
Part 1 PIK3CA mutant (n = 70) 6.5 versus 5.1 mo, p = 0.268 PIK3CA WT (n = 84) 5.8 versus 3.6 mo, p = 0.23 Part 2 PIK3CA mutant (n = 61) 5.4 versus 10.0 mo, p = 0.84 |
| Andrè, 2018 [46] |
SOLAR-1 | Phase III Double-blind Placebo-controlled Randomized 1:1 |
572 | Progressed on previous ET | ALP plus F500 versus PBO plus F500 |
PFS | PIK3CA-mutated (n = 341) 11.0 versus 5.7 mo, p < 0.001 |
| Baselga, 2018 [48] |
SANDPIPER | Phase III Double-blind Placebo-controlled Randomized 2:1 |
631 | Progressed on previous ET | TAS plus F500 versus PBO plus F500 |
PFS | 7.4 versus 5.4 mo, p = 0.0037 |
Abbreviations: ALP: alpelisib; BUP: buparlisib; CBR: clinical benefit rate; ET: endocrine therapy; EXE: exemestane; EVE: everolimus; F500: fulvestrant; HR: hazard ratio; mo: months; N: number; NSAIs: nonsteroidal aromatase inhibitors; NR: not reported; PBO: placebo; PFS: progression-free survival; PIC: pictlisib; TAM: tamoxifen; TAS: taselisib; WT: wild-type.