First author [year] [study name] | Treatment arms [n] | Key endpoint outcomes |
---|---|---|
Mouridsen H et al., 2001, 2003 [International Letrozole Breast Cancer Group]a [18, 19] | • Letrozole 2.5 mg OD [n = 453] • Tamoxifen 20 mg OD [n = 454] | Results at final 32 mos FU—Letrozole/tamoxifen TTP = 9.4/6.0 mos; p < 0.0001 OS = 34/30 mos; p = NS |
Bonneterre J et al., 2000 [TARGET]a [20] | • Anastrozole 1 mg OD [n = 340] • Tamoxifen 20 mg OD [n = 328] | Anastrozole/tamoxifen p = NS for all TTP = 8.2/8.3 mos |
Nabholtz JM et al., 2000 [the North American trial]a [21] | • Anastrozole 1 mg OD [n = 171] • Tamoxifen 20 mg OD [n = 182] | Anastrozole/tamoxifen TTP = 11.1/5.6 mos; p = 0.005 |
Paridaens RJ et al., 2008 [EORTC BCCG]a [22] | • Exemestane 25 mg OD [n = 182] • Tamoxifen 20 mg OD [n = 189] | Exemestane/tamoxifen PFS = 9.9/5.8 mos; p = 0.028 |
Robertson JF et al., 2016 [FALCON] [23] | • Fulvestrant 500 mg IM on days 0, 14, and 28, and every 28 days thereafter [n = 230] • Anastrozole 1 mg OD [n = 232] | Fulvestrant/anastrozole PFS: 16.6/13.8 mos; p = 0.05 PFS in patients with nonvisceral disease: 22.3/13.8 mos (hazard ratio, 0.59; 95% CI, 0.42–0.84) |
Bergh J et al., 2012 [FACT]a [24] | • Anastrozole 1 mg OD [n = 256] • Anastrozole 1 mg OD plus fulvestrant 500 mg IM on day 1 and 250 mg on days 15 and 29 of first cycle, and every fourth week thereafter [n = 258] | Fulvestrant + anastrozole/anastrozole TTP: 10.8/10.2 mos; p = NS OS: 37.8/38.2 mos; p = NS |
• Anastrozole 1 mg OD [n = 345] • Anastrozole 1 mg OD plus fulvestrant 500 mg IM on day 1 and 250 mg on days 14 and 28 of first cycle, and 28 days thereafter [n = 349] | Anastrozole/fulvestrant + anastrozole All patients PFS:13.5/15 mos; p = 0.007 Final OS: 42/49.8 mos; p = 0.03 Patients with no prior tamoxifen PFS:12.6/17 mos; p = 0.006 OS: 40.3/52.2 mos (HR 0.73, 95% CI 0.58–0.92) Patients with prior tamoxifen PFS: 14.1/13.5; p = 0.37 OS: 43.5/48.2 mos; p = 0.09 | |
Finn RS et al., 2016 [PALOMA-2] [27] | • Letrozole 2.5 mg OD [n = 222] • Letrozole 2.5 mg OD + palbociclib 125 mg OD for 3 weeks followed by 1 week off [n = 444] | Letrozole + palbociclib/letrozole: PFS: 24.8/14.5 mos; p < 0.001 |
Hortobagyi GN et al., 2016, 2018; O Shaughnessy J et al., 2018; Sonke GS et al., 2018 [MONALEESA-2] [28,29,30,31] | • Letrozole 2.5 mg OD + Placebo [n = 334] • Letrozole 2.5 mg OD + ribociclib 600 mg per day on a 3-weeks–on, 1-week–off schedule in 28-day treatment cycles [n = 334] | Letrozole + ribociclib/letrozole + placebo PFS: 25.3/16.0 mos; p < 0.0001 ORR: 42.5%/28.7%; p = 0.00009 De novo mBC patients PFS: Not reached/16.4 mos; HR, 0.45; 95% CI 0.27–0.75 Elderly patients (≥65 years) PFS: Not reached/18.4 mos; HR, 0.608; 95% CI 0.394–0.937 |
Goetz MP et al., 2015; Goetz MP et al., 2017; Johnston S et al., 2019 [MONARCH-3] [32,33,34] | • Anastrozole 1 mg or letrozole 2.5 mg OD + placebo [n = 165] • Anastrozole 1 mg or letrozole 2.5 mg OD + abemaciclib 150 mg orally every 12 h till progression [n = 328] | Abemaciclib + NSAI/NSAI + placebo PFS at interim analysis: Not reached/14.7 mos; p = 0.000021 Final PFS: 28.1/14.7 mos; p = 0.000002 ORR: 61%/45.5%; p = 0.003 |
Slamon DJ et al., 2018 [MONALEESA-3]c [35] | • Ribociclib 600 mg per day on a 3-weeks–on, 1-week–off schedule in 28-day treatment cycles + fulvestrant 500 mg IM on day 1 of each 28-day cycle, with an additional dose on day 15 of cycle 1 [total, n = 484; first-line setting, n = 238] • Fulvestrant + placebo [total, n = 242; first-line setting, n = 129] | Ribociclib + fulvestrant/fulvestrant + placebo: Overall PFS (first-line settings): 33.6/19.2 mos; HR 0.546, 95%CI 0.415–0.718 OS (first-line settings): Not reached/45.1 mos; HR 0.700, 95% CI 0.479–1.021 |
Tripathy D et al., 2018; Im SA et al., 2019 [MONALEESA-7]c [36] | • Ribociclib 600 mg per day on a 3-weeks–on, 1-week–off schedule in 28-day treatment cycles + oral tamoxifen (20 mg/day)/NSAI + goserelin [total, n = 335; first-line setting, n = 208] • Placebo + oral tamoxifen (20 mg/day)/NSAI + goserelin [total, n = 337; first-line setting, n = 196] | Overall: Ribociclib + endocrine therapy/placebo + endocrine therapy OS at 42 months: 70.2%/46.0%; p = 0.000973 Subgroup: Ribociclib + tamoxifen/placebo + tamoxifen PFS: 22.1/11 mos; hazard ratio 0.59; 95% CI 0.39–0.88 OS at 42 months: 71.2%/54.5%; hazard ratio 0.79; 95% CI 0.45–1.38 Subgroup: Ribociclib + NSAI/placebo + NSAI PFS: 27.5/13.8 mos; hazard ratio 0.57; 95% CI 0.44–0.74 OS at 42 months: 69.7%/43%; hazard ratio 0.70; 95% CI 0.50–0.98 |
Royce M et al., 2018 [BOLERO-4]c [37] | • Everolimus 10 mg/day + letrozole 2.5 mg/day [first-line setting, n = 202] | Everolimus + letrozole: PFS: 22 mos |
Beck JT et al., 2014 [Exploratory analysis of BOLERO-2] [38] | • Everolimus 10 mg OD + exemestane 25 mg OD [n = 100] • Exemestane 25 mg OD [n = 37] | Everolimus + exemestane/exemestane: PFS: 11.5/4.1 mos PFS [according to central assessment]: 15.2/4.2 mos |