Table 1.
Major published clinical trials of the combination of endocrine agents with RTK-targeting therapies for metastatic breast cancer
| RTK-targeting therapy | Study design | Patients | Key results | Reference |
|---|---|---|---|---|
| Anti-HER2 therapy | ||||
| Trastuzumab | ANA vs ANA + TRAS randomized phase III (TAnDEM study) | n = 207 | PFS: ANA + TRAS 4.8 month; ANA 2.4 month; HR, 0.63; 95% CI, 0.47–0.84; P = 0.016 OS: ANA + TRAS 28.5 month; ANA 23.9 month; P = 0.325 70% of patients in the ANA arm crossed over to TRAS after progression OS: without crossover usage of TRAS ANA + TRAS 28.5 month; ANA 17.2 month; P = 0.048 CBR: ANA + TRAS 42.7%; 95% CI, 33.0–52.9%; ANA 27.9%; 95% CI, 19.5–37.5%; P = 0.026 | Kaufman et al.(45) |
| Lapatinib | LET vs LET + LAP randomized phase III | Overall, n = 1286 HER2 positive, n = 219 | HER2+ cases PFS: LET + LAP 8.2 month; LET + placebo 3.0 month; HR, 0.71; 95% CI, 0.53–0.96; P = 0.019 OS: LET + LAP 33.3 month; LET + placebo 32.3 month; HR, 0.74; 95% CI, 0.5–1.1; P = 0.113 CBR: LET + LAP 48%; LET + placebo 29%; OR, 0.4; 95% CI, 0.2–0.8; P = 0.003 | Johnston et al.(46) |
| mTOR inhibitors | ||||
| Everolimus | TAM vs TAM + EVE randomized phase II (GINECO study) | After prior AI, n = 111 | CBR: TAM + EVE 61%; TAM 42%; P = 0.045 TTP: TAM + EVE 8.6 month; TAM 4.5 month; HR, 0.54; 95% CI, 0.36–0.81; P = 0.0002 Exploratory subgroup analysis in patients with secondary hormone resistance CBR: TAM + EVE 74%; TAM 48% TTP: TAM + EVE 14.8 month; TAM 5.5 month; HR, 0.46; 95% CI, 0.26–0.83; P = 0.0087 | Bachelot et al.(48) |
| EXE vs EXE + EVE randomized phase III (BOLERO-2 clinical trials) | Previously treated with NSAI in the adjuvant setting or for advanced disease (or both), n = 724 Asian patients, n = 143 | Median PFS: Local assessment: EXE + EVE 6.9 months; EXE + placebo 2.8 month; HR, 0.43; 95% CI, 0.35–0.54; P < 0.001 Central assessment: EXE + EVE 10.6 months; EXE + placebo 4.1 month; HR, 036; 95% CI, 0.27–0.47; P < 0.001 Asian patients: EXE + EVE 8.48 month; EXE + placebo 4.14 month; HR, 0.62; 95% CI, 0.41–0.94; P < 0.001 | Baselga et al.(47) | |
| Temsirolimus | LET vs LET + TEM randomized phase III | AI naïve, first-line, n = 1112 | PFS: LET + TEM 8.9 month; LET + placebo 9 month; HR, 0.90; 95% CI, 0.76–1.07; P = 0.25 OS: both NE; HR, 089; 95% CI, 0.65–1.23; P = 0.50 | Wolff et al.(49) |
Where available, P-values are indicated. AI, aromatase inhibitors; ANA, anastrozole; CBR, clinical benefit rate; CI, confidence interval; EVE, everolimus; HR, hazard ratio; LAP, lapatinib; LET, letrozole; mTOR, mammalian target of rapamycin; NE, not estimable; NSAI, non-steroidal aromatase inhibitor; OR, odds ratio; OS, overall survival; EXE: exemestane; PFS, progression-free survival; RTK, receptor tyrosine kinase; TAM, tamoxifen; TEM, temsirolimus; TRAS, trastuzumab; TTP, time-to progression.