. 2017 Jun 19;9(7):465–479. doi: 10.1177/1758834017711097

Table 1.

Phase II/III. Clinical studies with fulvestrant.

Trial	Phase	Menopausal status	n	Regimen	Treatment line	Primary endpoint	CBR or ORR (%)	Survival (months)
Trial	Phase	Menopausal status	n	Regimen	Treatment line	Primary endpoint	CBR or ORR (%)	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.