Table 2.
Prospective Randomized Trials Testing Combinations of PI3K Pathway Inhibitors and Endocrine Therapies
| Kinase Target | Trial Design | Phase | Reference |
|---|---|---|---|
| mTOR | Letrozole ± everolimus in patients with early-stage ER-positive breast cancer | II | Baselga et al15 |
| Exemestane ± everolimus in ER-positive metastatic breast cancer after progression while receiving another AI | III | NCT00863655 (BOLERO-2; ongoing) | |
| Tamoxifen ± everolimus in ER-positive metastatic breast cancer after progression while receiving AI | II | TAMRAD; Bachelot et al79 | |
| HER2 | Anastrozole ± trastuzumab in patients with ER-positive/HER2-positive metastatic breast cancer | III | Kaufman et al95 |
| HER2/EGFR | Letrozole ± lapatinib in ER-positive metastatic breast cancer | III | Johnston et al94 |
| AI ± lapatinib or AI + fulvestrant ± lapatinib in ER-positive metastatic breast cancer after progression while receiving AI | III | NCT00688194 (ongoing) | |
| AI ± trastuzumab or lapatinib or both in patients with ER-positive/HER2-positive metastatic breast cancer | III | NCT01160211 (not yet open) | |
| EGFR | Anastrozole ± gefitinib in early-stage ER-positive breast cancer | II | Smith et al121 |
| Anastrozole ± gefitinib in metastatic ER-positive patients | II | Cristofanilli et al122 | |
| PKCβ, PDK1, p70S6K | Fulvestrant ± enzastaurin in ER-positive metastatic breast cancer after progression while receiving AI | II | NCT00451555 (ongoing) |
| Farnesyl transferase | Letrozole ± tipifarnib in ER-positive metastatic breast cancer after progression on tamoxifen | II | Johnston et al123 |
| IGF-1R/InsR | BMS-754807 ± letrozole in ER-positive metastatic breast cancer after progression while receiving AI | II | NCT01225172 (ongoing) |
| IGF-1R | IMCA12 ± same antiestrogen (AI, fulvestrant, or tamoxifen) after progression in patients with ER-positive metastatic breast cancer | II | NCT00728949 (ongoing) |
| AI or fulvestrant ± AMG479 in ER-positive advanced or metastatic breast cancer after progression while receiving endocrine Tx | II | Kaufman et al124 |
Abbreviations: AI, aromatase inhibitor; BOLERO, Breast cancer trials of OraL EveROlimus; EGFR, epidermal growth factor receptor; ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; IGF-1R, insulin-like growth factor-1 receptor; InsR, insulin receptor; mTOR, mammalian target of rapamycin; PI3K, phosphatidylinositol 3-kinase; PKC, protein kinase C; TAMRAD, Tamoxifen and RAD001.