Table 1.
Trial | Phase | Menopausal status | n | Regimen | Treatment line | Primary endpoint | CBR or ORR (%) | Survival (months) | |
---|---|---|---|---|---|---|---|---|---|
OS | PFS or TTP | ||||||||
Fulvestrant single agent | |||||||||
CONFIRM Di Leo et al.15,16
[2010, 2014] |
III | Postmenopausal | 736 | Fulvestrant 500 mg, fulvestrant 250 mg |
Second | TTP | 45.6 versus 39.6 (CBR) | 26.4 versus 22.3 p = 0.02 | 6.5 versus 5.5 p = 0.006 |
FIRST Robertson et al.18–20 [2009, 2012, 2015] Ellis et al.21 [2015] |
II | Postmenopausal | 205 | Fulvestrant 500 mg, anastrozole 1 mg |
First | CBR | 72.5 versus 67.0 (CBR) p = 0.386 |
54.1 (n = 86) versus 48.4 (n = 84) p = 0.04 | 23.4 versus 13.1 p = 0.01 |
FALCON Robertson et al.22 [2017] | III | Postmenopausal | 462 | Fulvestrant 500 mg, anastrozole 1 mg |
First | PFS | 78 versus 74 (CBR) p = 0.3045 |
NR | 16.6 versus 13.8 p = 0.0486 |
Fulvestrant in combination with other endocrine therapy | |||||||||
FACT Bergh et al.23 [2012] | III | Postmenopausal | 514 | Fulvestrant 250 mg + anastrozole, anastrozole |
First | TTP | NR | 38.2 versus 37.8 p = 1.00 | 10.8 versus 10.2 p = 0.91 |
SWOG 0226 Mehta et al.24 [2012] |
III | Postmenopausal | 694 | Fulvestrant 250 mg + anastrozole, anastrozole, fulvestrant |
First | PFS | 73 versus 70 (CBR) | 47.7 versus 41.3 p = 0.05 | 15 versus 13.5 p = 0.007 |
Fulvestrant in combination with targeted agents
fulvestrant + CDK inhibitor | |||||||||
PALOMA 3 Turner et al.34 [2015] Cristofanilli et al.35 [2016] |
III | Pre/peri/ postmenopausal |
521 | Fulvestrant 500 mg + palbociclib, Fulvestrant 500 mg + placebo |
Second | PFS | 24.6 versus 10.9 (CBR) p = 0·0012 |
NR | 9.5 versus 4.6 p < 0.001 |
Fulvestrant + mTOR inhibitor | |||||||||
PrECOG 0102 Kornblum et al.36 [2016] |
II | Postmenopausal | 131 | Fulvestrant 500 mg + everolimus, fulvestrant 500 mg + placebo |
Second | PFS | NR | 24.8 not reached in the placebo arm |
10.4 versus 5.1 p = 0.02 |
Fulvestrant + pan-PI3K inhibitor | |||||||||
BELLE 2 Baselga et al.37 [2015] |
III | Postmenopausal | 1147 | Fulvestrant 500 mg + buparlisib, fulvestrant 500 mg + placebo |
Second | PFS | 11.8 versus 7.7 (ORR) | NR | 6.9 versus 5.0 p < 0.001 |
FERGI Krop et al.39 [2016] |
II | Postmenopausal | 168 | Fulvestrant 500 mg + pictilisib, fulvestrant 500 mg + placebo |
Second | PFS | 7.9 versus 6.3 (ORR) | NR | 6.6 versus 5.1 p = 0.096 |
BELLE 3 Di Leo et al.38 [2016] | III | Postmenopausal | 432 | Fulvestrant 500 mg + buparlisib, fulvestrant 500 mg, fulvestrant 500 mg + placebo |
Second | PFS | 7.6 versus 2.1 (ORR) |
7.6 versus 2.1 | 3.9 versus 1.8 p < 0.001 |
LEA Martín et al.40 [2015] |
III | Postmenopausal | 380 | Fulvestrant 250 mg or letrozole + bevacizumab, fulvestrant 250 mg or letrozole + placebo |
First | PFS | 76.8 versus 67.4 (CBR) p = 0.041 | 52.1 versus 51.8 p = not stated | 19.3 versus 14.4 p = 0.126 |
Fulvestrant + EGFR, HER2 inhibitor | |||||||||
CALGB 40302 Burstein et al.41 [2014] |
III | Postmenopausal | 291 | Fulvestrant 500 mg + lapatinib, fulvestrant 500 mg + placebo | First | PFS | NR | 30 versus 26.4 p = 0.25 | 4.7 versus 3.8 p = 0.37 |
Fulvestrant + IGFR inhibitor | |||||||||
Robertson et al.42 [2013] | II | Postmenopausal | 156 | Fulvestrant 250 mg or exemestane + ganitumab, fulvestrant 250 mg or exemestane + placebo |
Second | PFS | NR | 22.2 not reached p = 0.025 favours placebo |
5.7 versus 3.9 p = 0.44 |
Fulvestrant + RET, VEGFR and EGFR TKI inhibitor | |||||||||
OCOG -ZAMBONEY Clemons [2014] | II | Postmenopausal | 129 | Fulvestrant 500 mg + vandetanib, fulvestrant 500 mg + placebo |
First | PFS | NR | 73.7 versus 69.1 | 6 versus 4.8 p = 0.47 |
CDK, cyclin-dependent kinase; CBR, clinical benefit rate; ORR, overall response rate; EGFR, epidermal growth factor receptor; HER2, human epidermal growth factor receptor type 2; IGFR, insulin-like growth factor receptor; mTOR, mammalian target of rapamycin; N, number of patients; NR, not reported; NS, not significant; OS, overall survival; PFS, progression-free survival; PI3K, phosphoinositide 3-kinase; RET, rearranged during transfection; TKI, tyrosine kinase inhibitor; TTP, time to progression; VEGFR, vascular endothelial growth factor receptor.