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.