Clinical setting | Trial phase | Intervention | Clinical endpoints | Biological correlates | Ref. |
---|---|---|---|---|---|
MBC: hormone-refractory | II (N = 15) | ANA + GEF | PR = 0 SD = 0 | NA | [19] |
Neoadjuvant PBC | II RCT (N = 188) | ANA versus ANA + GEF for 16 weeks | ORR = 61% versus 48%, p = 0.067 | Reduction in Ki67 = 83.6% versus 77.4%, p = 0.164 | [20] |
Preoperative PBC: EGFR+ only | II RT (N = 56) | GEF versus GEF + ANA for 4–6 weeks | ORR = 50% versus 54% | Reduction in Ki67 = 92.4% versus 98%, p = 0.005 Reduction in pER, pMAPK and pEGFR similar in both groups | [21] |
Combination with trastuzumab | |||||
HER2+ MBC (note: all patients were TRAS and AI naïve, 18% were IHC2+/FISH-) | II (N = 33) | TRAS + LET | PR = 26% SD = 26% | NA | [29] |
HER2 MBC (all patients were IHC 3+ or FISH+) | III RCT (N = 207) | ANA versus ANA + TRAS | PFS = 2.4 months versus 4.8 months, p = 0.0016 OS = 23.9 months versus 28.5 months, p = 0.325 Among 147 evaluable patients: ORR = 6.8% versus 20.3%, p = 0.018 | NA | [31] |
Combination with lapatinib | |||||
MBC: included other hormone sensitive advanced cancers | I (N = 17) | LAP + LET | 4 SD including 1 breast cancer | NA | [36] |
Combination with farnesyltransferase inhibitors: tipifarnib | |||||
MBC: hormone resistant | I (N = 12) | TAM + TIP | PR = 2/12 SD > 6 months = 1/12 | NA | [42] |
MBC: tamoxifen resistant | I (N = 20) | TAM + TIP | PR = 1/20 SD > 4 months = 6/20 SD > 6 months = 4/20 | NA | [41] |
MBC: tamoxifen resistant | II RCT (N = 120) | LET versus | PR = 38% versus 30% | NA | [43] |
 |  | LET + TIP | SD = 38% versus 39% |  |  |
Combination with mTOR inhibitors: everolimus and temsirolimus | |||||
MBC: stable or slowly progressing on letrozole. | Ib (N = 9) | LET + EVE 1, 5 or10 mg daily | No grade 3–4 toxicitiesat 5 mg (6 patients) or10 mg (3 patients) | NA | [50] |
MBC | II (N = 92) | LET versusLET+TEM 10 mgdaily versusLET+TEM 30 mgintermittent | ORR = 45% versus33% versus 40%PFS = 11.6 monthsversus 11.5 monthsversus 13.2 months | NA | [51] |
MBC | III RCT (N = 992) | LET versusLET + TEM intermittent | ORR = 24% versus 24%SD = 19% versus 16%PFS = 9.2 months versus9.2 months | NA | [52] |
Combination with angiogenesis inhibitors: bevacizumab | |||||
MBC | II (N = 25) | LET + BEV | PR = 2/25SD > 6 months = 13/25SD < 6 months = 4/25PD = 6/25 | NA | [57] |