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. 2016 Aug 16;1(4):e000062. doi: 10.1136/esmoopen-2016-000062

Table 1.

Summary of randomised phase II and III studies comparing third-generation aromatase inhibitors or fulvestrant with an antioestrogen, megestrol acetate or a first-generation aromatase inhibitor

Reference Treatment* Number of patients Patient population Phase Prior endocrine therapy Prior chemotherapy for ABC RR (%) (95% CI) SD (%) (95% CI) TTP/PFS (median; months) (95% CI) OS (median; months) (95% CI)
First-line therapy
NSAIs vs tamoxifen
 Bonneterre et al6 8 Anastrozole 340 ER/PGR+ (UK 54/56%) III (TARGET) None: 89/88%; >12 months adj TAM: 11/12% None 32.9 23.2 8.2; ER/PGR+: 8.9 NR
Tamoxifen 328 32.6 22.9 8.3 (p=0.941); ER/PGR+: 7.8
 Nabholtz et al7 9 Anastrozole 171 ER+ (UK 11/11%) III (NAT) None: 82/79%; >12 months adj TAM: 18/21% None 21 38.0 11.1 NR
Tamoxifen 182 17 28.6 5.6 (p=0.005)
 Milla-Santos et al10 Anastrozole 121 ER+ III None None 35 47 18.0 17.4
Tamoxifen 40 mg 117 26 (p=0.172) 29 7.0 (HR 0.13; p<0.01) 16.0 (HR 0.64; p=0.003)
 Mouridsen et al12–14 Letrozole 453 ER/PGR+ (UK 34/33%) III None: 81/82% >12 months adj TAM: 19/18% ≤1 30 49 (44 to 54) (CBR) 9.4 34
Tamoxifen 454 20 (OR 1.71; 1.26 to 2.31; p=0.0006) 38 (34 to 43) 6.0 (p=0.0001) 30 (p=0.53)
SAI vs tamoxifen
 Paridaens et al15 16 Exemestane 182 Hormone receptor+ (UK 8/5%) II/III None: 79/61%; >6 months adj TAM: 21/21% ≤1 46 29.7† 9.9 (8.7 to 11.8) p=0.821
Tamoxifen 189 31 (OR 1.85; 1.21 to 2.82; p=0.005) 35.4 5.8 (5.3 to 8.1) (HR 0.84; p=0.121)
Fulvestrant vs tamoxifen
 Howell 2004 et al17 Fulvestrant 250 mg 313 ER/PGR+ (UK 18/20%; ER−/PGR− 1/1%) III None: 78/75%; >12 months adj TAM: 22/25% None 31.8 54.3† (CBR) 6.8 36.9 (estimated)
Tamoxifen 274 33.9 (OR 0.87; 0.61 to 1.24; p=0.45) 62.0 (p=0.026) 8.3 (HR 1.18; p=0.088) 38.7 (HR 1.29; p=0.04)
First-line or second-line therapy
NSAIs vs megestrol acetate
 Buzdar et al18 Anastrozole 1 mg 128 ER+ or prior sensitivity to TAM (UK 13/15/13%) III PD on antioestrogen‡; adj antioestrogen: 47/42/39% ≤1 10 27 5.6 NR
Anastrozole 10 mg 130 6 24 4.7
Megestrol acetate 128 6 30 4.9
 Jonat et al19 Anastrozole 1 mg 135 ER/PGR+ (UK 34/39/38%) III PD after/on TAM; adj TAM: 49/39 /42%; first-line TAM: 51/61/58% ≤1 34.1 34.0 (CBR) NR NR
Anastrozole 10 mg 118 33.9 33.9
Megestrol acetate 125 32.8 32.8
 Buzdar et al21 Letrozole 0.5 mg 202 ER/PGR+ (UK 13/15/13%) III PD on antioestrogen‡; adj antioestrogen: 47/42/39%; first-line antioestrogen: 53/58/61% ≤2 21 (15.2 to 26.4) 12.4 5.6 (3.3 to 6.3) 33.1 (26.7 to 39.4)
Letrozole 2.5 mg 199 16 (11.0 to 21.2) 10.6 3.2 (3.0 to 5.3) 26.6 (25.0 to 33.8)
Megestrol acetate 201 15 (10.0 to 19.9) 8.5 3.4 (3.0 to 5.6) 26.2 (21.7 to 29.9)
 Dombernowsky et al22 Letrozole 0.5 mg 188 ER/PGR+ (UK 45/43/41%) III PD on antioestrogen‡; adj antioestrogen: 35/33/32% ≤1 13 (p=0.004) 14.4 5.1 (p=0.02) 1.34 (risk ratio)
Letrozole 2.5 mg 174 24 10.9 5.6 (p=0.07) 0.82
Megestrol acetate 189 16 (p=0.04) 15.3 5.5 1.12
SAI vs megestrol acetate
 Kaufmann et al23 Exemestane 366 ER/PGR+ (UK+or prior sensitivity to TAM (UK 33/32%) III PD on TAM‡; adj TAM: NR ≤1 15 37.4 (CBR) 4.5 Not reached
Megestrol acetate 404 012.4 (NS) 34.6 (NS) 3.7 (p=0.037) 27.4(p=0.039)

For RR, SD, duration of TTP/PFS and OS, the number of decimals reported by the authors is given.

ER/PGR+, HER2: numbers are given when possible.

*Unless stated, doses of tamoxifen, megestrol acetate, anastrozole, letrozole and exemestane were 20, 160, 1, 2.5 and 25 mg, respectively.

†Duration of SD not reported; if not marked, duration of SD reported ≥24 weeks or 6 months.

‡Defined as relapse on adjuvant antioestrogen or within 12 months of stopping treatment or progression on first-line antioestrogen therapy.

ABC, advanced breast cancer; Adj, adjuvant; AI, aromatase inhibitor; CBR, clinical benefit rate; ER, oestrogen receptor; HER2, human epidermal growth factor receptor 2; NR, not reported; NS, non-significant; NSAI, non-steroid aromatase inhibitor; PD, progressive disease; PFS, progression-free survival; PGR, progesterone receptor; RR, response rate; SAI, steroid aromatase inhibitor; TAM, tamoxifen; TARGET, Tamoxifen or ‘Arimidex’ Randomized Group Efficacy and Tolerability; TTP, time to progression; OS, overall survival; UK, unknown.