Table 2.
Summary of randomised phase II and III studies comparing the individual aromatase inhibitors with each other, with fulvestrant, or combinations
| 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 | ||||||||||
| Exemestane vs anastrozole | ||||||||||
| Iwata et al24 | Exemestane | 149 | ER/PGR+ (HER2− 94/94%) | III | None: 83/83%; >12 months adj TAM: 17/17% | None | 43.8 (35.3 to 52.8) | 31.1 | 13.8 (10.8 to 16.59 | NR |
| Anastrozole | 149 | 39.1 (30.6 to 48.1) | 38.3 | 11.1 (10.8 to 16.6) | ||||||
| Llombart-Cussac et al25 | Exemestane | 51 | ER/PGR+ (UK 0/4%) | II, randomised | None: 49/50%; >24 months adj TAMs: 51/50% | ≤1 | 36.2 (18.5 to 45.9) | 59.6 (CBR) | 6.1 (2.4 to 9.6) | 19.9 (15.32 to 24.46) |
| Anastrozole | 52 | 46.0 (32.2 to 59.8) | 68 | 12.1 (7.3 to 16.8) (HR 1.13; p=0.558) | 48.3 (18.3 to 78.3) (HR 1.33; p=0.296) | |||||
| Fulvestrant vs anastrozole | ||||||||||
| Robertson et al26 27 | Fulvestrant 500 mg | 102 | ER/PGR+ (UK 1/3%) (HER2 2+/3+ 19/18%) | III (FIRST) | None: 72/78%; adj endocrine therapy: 28/22% | None | 31.4 | 41.2 | 23.4 | NR |
| Anastrozole | 103 | 31.1 | 35.0 | 13.1 (HR 0.66; p=0.01) | ||||||
| Combination therapy vs single agent | ||||||||||
| Bergh et al28 | Fulvestrant 250 mg+anastrozole | 258 | ER/PGR+ | III (FACT) | None: 30/34%; adj TAM: 70/67%; adj AI: 2/1% | None | 31.8 | 55.0 (CBR) | 10.8 | 37.8 |
| Anastrozole | 256 | 33.6 (OR 0.92; p=0.76) | 55.1 (OR 1.0; p=0.99) | 10.2 (HR 0.99; p=0.91) | 38.2 (HR 1.0; p=1.00) | |||||
| Mehta et al29 | Anastrozole+fulvestrant 250 mg | 349 | ER/PGR+ HER2+ 10/9% | III (SWOG 0226) | None: 60/60%; >12 months adj TAM: 40/40% | None | 27 | 73† | 15.0 (13.2 to 18.4) | 47.7 (43.4 to 55.7) |
| Anastrozole → fulvestrant (41%) | 345 | 22 (p=0.26) | 70 (p=0.39) | 13.5 (12.1 to 15.1) (HR 0.80; p=0.007) | 41.3 (37.2 to 45.0) (HR 0.81; p=0.049) | |||||
| First-line or second-line therapy | ||||||||||
| Letrozole vs anastrozole | ||||||||||
| Rose et al30 | Letrozole | 356 | ER/PGR+ (UK 21/8%) | IIIb/IV | PD‡ on antioestrogen; adj antioestrogen: number NR | ≤1 | 19.1 (15.7 to 22.9) | 7.9 | 5.7 (5.1 to 6.0) | NR |
| Anastrozole | 357 | 12.3 (9.6 to 15.6) (p=0.013) | 10.6 | 5.7 (4.6 to 6.1) (p=0.92) | ||||||
| Fulvestrant vs AIs | ||||||||||
| Howell et al31 | Fulvestrant 250 mg | 222 | ER/PGR+ or prior sensitivity to endocrine therapy (UK 23/16%) | III | PD on adj: 56/56%; PD on first-line endocrine therapy: 44/44% no prior AI | ≤2 | 20.7 | 23.9 | 5.5 | NR |
| Anastrozole | 229 | 15.7 | 29.3 | 5.1 | ||||||
| Xu et al32 | Fulvestrant 250 mg+placebo | 121 | ER+ | III | PD after adj: NR; PD on first-line antioestrogen therapy: NR | ≤2 | 10 | 48.2† (CBR) | 3.6 | NR |
| Anastrozole+placebo | 113 | 14 | 36.1 (OR 0.608; p=0.117) | 5.2 (HR 1.314; p=0.101) | ||||||
| Robertson et al33 | Fulvestrant 250 mg+placebo | 206 | ER/PGR+ or prior sensitivity to endocrine therapy (UK 6/8%) (ER/PGR− 7/5%) | III | PD on adj antioestrogen therapy: 56/50%; PD on first-line endocrine therapy: 44/50% | No criteria | 17.5 | 24.8 | 5.4 | NR |
| Anastrozole+placebo | 194 | 17.5 | 18.6 | 3.4 (HR 0.92; p=0.43) | ||||||
| Robertson et al33 | Fulvestrant 250 mg | 428 | ER/PGR+ or prior sensitivity to endocrine therapy (UK 15/12%) (ER/PGR− 5/5%) | Combined data from two phase III (0020 and 0021) | PD after adj endocrine therapy: 57/56%; PD on first-line endocrine therapy: 43/44% | NR | 19.2 | 24.3 | NR | NR |
| Anastrozole | 423 | 16.5 (p=0.32) | 24.3 | |||||||
| Chia et al34 | Fulvestrant 250 mg | 351 | ER/PGR+ | III (EFECT) | PD on NSAI‡; 60% ≥2 lines | ≤1 | 7.4 | 32.2 (CBR) | 3.7 | NR |
| Exemestane | 342 | 6.7 (OR 1.12; p=0.736) | 31.5 (OR 1.03; p=0.853) | 3.7 (HR 0.963; p=0.6531) | ||||||
| Combination therapy vs single agent | ||||||||||
| Johnston et al35 | Fulvestrant+anastrozole | 243 | ER/PGR+ HER2− (HER2+ 7/6/7%) (HER2 UK 43/33/36%) | III (SoFEA) | PD on adj NSAI: 17/22/17% first-line NSAI: 83/78/83% | ≤1 | 8 | 33 | 4.4 (3.4 to 5.4) | 20.2 (17.2 to 22.5) |
| Fulvestrant+placebo | 231 | 8 | 31 | 4.8 (3.6 to 5.5) | 19.4 (16.8 to 22.8) | |||||
| Exemestane | 249 | 4 (NS) | 23 (NS) | 3.4 (3.0 to 4.6) (NS) | 21.6 (19.4 to 23.9) (NS) | |||||
For RR, duration of TTP/PFS and OS, the number of decimals used by the authors is reported. ER/PGR+, HER2: % positive are given when possible.
*Doses of anastrozole, letrozole and exemestane were 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 NSAI or within 6 months of stopping treatment or by progression on NSAI for advanced breast cancer.
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; TAM, tamoxifen; TTP, time to progression; OS, overall survival; UK, unknown.