Table 1.
Results of key clinical trials
| Study | Study design | Patients | Treatments | Primary endpoint | Secondary endpoints |
|---|---|---|---|---|---|
| ER-positive, HER2-negative advanced BC | |||||
| Wolff et al14 (HORIZON) | Placebo-controlled, randomized, Phase III | Postmenopausal AI-naïve, ER-positive, advanced BC, first-line (n=1,112) | Letrozole 2.5 mg daily, temsirolimus 30 mg daily, 5 days every 2 weeks or letrozole 2.5 mg daily + placebo | Median PFS 9 versus 8.9 months (comparable) | Median OS not reached (comparable) ORR 27% versus 27% SD at least 24 weeks 17% versus 19% |
| Bachelot et al16 (TAMRAD) | Randomized, open, Phase II | Postmenopausal AI-resistant, ER-positive, HER2-negative, metastatic BC (n=111) | Tamoxifen 20 mg daily + everolimus 10 mg daily or tamoxifen 20 mg daily | 6 month CBR 61% versus 42% (exploratory analysis) |
TTP 8.6 versus 4.5 months Risk of death HR 0.45 |
| Yardley et al19 (BOLERO-2) | Placebo-controlled, randomized Phase III | Postmenopausal NSAI-resistant, ER-positive, HER2-negative, advanced BC (n=724) | Exemestane 25 mg daily + everolimus 10 mg daily or exemestane 25 mg daily + placebo | Median PFS 7.8 versus 3.2 months investigator review difference statistically significant |
Median PFS 11 versus 4.1 months central review OS events 25.4% versus 32.2% ORR 12.6% versus 2.1% CBR 49.9% versus 22.2% |
| HER2-positive advanced BC | |||||
| O’Regan et al28 BOLERO-3 |
Placebo-controlled, randomized Phase III | HER2-positive advanced BC, prior taxane required, trastuzumab-resistant (n=569) | Vinorelbine 25 mg/m2 weekly + trastuzumab 2 mg/kg/week + everolimus 5 mg daily or vinorelbine 25 mg/m2 weekly + trastuzumab 2 mg/kg/week + placebo | Median PFS 7 versus 5.78 months (difference statistically significant) |
ORR 40.8% versus 37.2% CBR 59.2% versus 53.3% OS events 36.3% versus 41.1% |
| ER-positive BC : neoadjuvant therapy | |||||
| Baselga et al15 | Placebo-controlled, randomized Phase II | Postmenopausal operable ER-positive (n=270) | Letrozole 2.5 mg daily + everolimus 10 mg daily or letrozole 2.5 mg daily + placebo (4 months) | Clinical RR 68.1% versus 59.1% (difference statistically significant) | Antiproliferative response day 15 (downregulation of Ki67 expression) 57% versus 30% RR 58% versus 47% (ultrasound) RR 36.2% versus 39.4% (mammography) |
Abbreviations: ER, estrogen receptor; BC, breast cancer; RR, response rate; HER2, human epidermal growth factor 2 receptor; AI, aromatase inhibitor; PFS, progression-free survival; OS, overall survival; CBR, clinical benefit rate; TTP, time to progression; HR, hazard ratio; NSAI, non-steroidal aromatase inhibitor; ORR, overall response rate; SD, stable disease.