Skip to main content

Table 2 Summary of key studies for the second-line management of women with HR+, HER2– or unknown HER2 status mBC

From: Optimizing treatment selection, and sequencing decisions for Management of HR-Positive, HER2-Negative advanced breast cancer – Proceedings from breast cancer expert group meeting

First author [year] [reference] [study name]

Treatment arms [n]

Key endpoint outcomes

Chia S et al., 2008 [EFECT]a,b [77]

• Fulvestrant 500 mg IM on day 1, and 250 mg on days 14, and 28, and every 28 days thereafter [total, n = 351; second-line setting, n = 313]

• Exemestane 25 mg OD [total, n = 342; second-line setting, n = 294]

Fulvestrant/exemestane

TTP: 3.7 mos in both groups

Di Leo A et al., 2010, 2014 [CONFIRM]a,b [79, 80]

• Fulvestrant 500 mg IM on days 0, 14, and 28, and every 28 days thereafter [total, n = 362; second-line setting, n = 136]

• Fulvestrant 250 mg IM every 28 days [total, n = 374; second-line setting, n = 177]

Fulvestrant 500 mg/fulvestrant 250 mg

PFS: 6.5/5.5 mos; p = 0.006

OS [final analysis]: 26.4/22.3 mos; p = 0.02

Turner NC et al., 2015; Cristofanilli M et al.,2016; Turner NC et al. 2018 [PALOMA-3]c [43, 51, 52]

• Fulvestrant 500 mg IM on days 1, 15, and 29 of the first cycle, and every 28 days thereafter + palbociclib 125 mg for 3 wks followed by 1 wk. off [n = 347]

• Placebo + Fulvestrant [same as Fulvestrant dose in combination] [n = 174]

Fulvestrant + palbociclib/placebo + fulvestrant: Results at final analysis

PFS: 9.5/4.6 mos; p < 0.0001

OS: 39.7/29.7 mos; Hazard ratio, 0.72; 95% CI, 0.55–0.94

Sledge GW Jr. et al., 2017; Sledge GW Jr. et al., 2019 [MONARCH-2]b [53, 54]

• Fulvestrant 500 mg IM on days 1 and 15 of the first cycle, and every 28 days thereafter + abemaciclib 200 mg twice-daily, during each 28-day cycle, tapered later to 150 mg [total, n = 446; second-line setting, n = 171]

• Fulvestrant [same as above] + placebo twice-daily [total, n = 223; second-line setting, n = 85]

Fulvestrant + abemaciclib/fulvestrant + placebo

PFS: 16.9/9.3 mos; p < 0.0001

OS: 46.7/37.3 mos; p = 0.013

Slamon DJ et al., 2018 [MONALEESA-3]b [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; second-line setting, n = 236]

• Fulvestrant + placebo [total, n = 242; second-line setting, n = 109]

Ribociclib + fulvestrant/fulvestrant + placebo

Overall PFS (early relapse + second-line settings): 14.6/9.1 mos; HR 0.571, 95% CI 0.443–0.737

OS (early relapse + second-line settings): 40.3/32.5 mos; HR 0.730, 95% CI 0.530–1.004

Kornblum N et al., 2018 [PrE0102] [total, n = 131]b [67]

• Fulvestrant (500 mg on day 1 and day 15 of cycle 1, followed by day 1 of cycles 2 and beyond) + everolimus 10 mg OD

• Fulvestrant + Placebo

Fulvestrant + everolimus/fulvestrant + placebo

PFS: 10.3/5.1 mos; p = 0.02

CBR: 63.6%/41.5%; p = 0.01

Baselga J et al., 2012, Yardley DA et al., 2013, Piccart M et al., 2014 [BOLERO-2] [81,82,83]

• Everolimus 10 mg OD + exemestane 25 mg OD [n = 485]

• Exemestane 25 mg OD [n = 239]

Everolimus + exemestane/exemestane:

PFS [by investigator review]: 7.8/3.2 mos; p < 0.0001

OS: 31/26.6 mos; p = NS

Jerusalem G et al., 2018 [BOLERO-6] [84]

• Everolimus 10 mg/day + exemestane 25 mg/day [n = 104]

• Everolimus 10 mg/day [n = 103]

• Capecitabine 1250 mg/m2 twice daily [n = 102]

Everolimus + exemestane/everolimus/capecitabine

PFS: 8.4/ 6.8/ 9.6 mos (everolimus + exemestane vs. everolimus: HR, 0.74; 90% CI, 0.57–0.97)

OS: 23.1/ 29.3 mos; Hazard ratio, 1.27; 90% CI, 0.95–1.70

Royce M et al., 2018 [BOLERO-4]b [37]

• Everolimus 10 mg/day + exemestane 25 mg/day [second-line setting, n = 50]

PFS in second-line setting: 3.7 mos

Tesch H et al., 2019 [4EVER] [85]

• Everolimus 10 mg/day + exemestane 25 mg/day [total n = 299; efficacy evaluation, n = 281]

ORR (24 weeks): 8.9% (95% CI, 5.8–12.9%)

PFS: 5.6 mos (95% CI, 5.4–6.0 mos)

Cazzaniga ME et al., 2017 [EVA] [total, n = 404]b [86]

• Everolimus 10 mg/day + exemestane 25 mg/day

ORR noted in 31.6% of patients

Disease control rate noted in 60.7% of patients

Safra T et al., 2018 [87]

• Everolimus 10 mg/day + letrozole 2.5 mg/day [n = 72]

PFS: 8.8 mos; 95% CI, 6.6–11.0 mos

OS: 22.9 mos; 95% CI, 18.5–28.9 mos

Dickler MN et al., 2017 [MONARCH-1] [76]

• Abemaciclib 200 mg orally every 12 h till disease progression or acceptable toxicity [n = 132]

PFS: 6 mos; 95% CI, 4.2–7.5

OS: 17.7 mos; 95% CI, 16.0–Not reached

Andre F et al., 2019 [SOLAR-1] [total, n = 572] [12]

• Alpelisib (300 mg/day) + fulvestrant (500 mg every 28 days and once on day 15)

• Fulvestrant + placebo

Alpelisib + fulvestrant vs. fulvestrant + placebo

Investigator-assessed PFS: 11 vs. 5.7 mos; p < 0.001

Overall response in patients with PIK3CA mutations: 26.6% vs. 12.8%

  1. HR Hormone receptor, HER Human epidermal growth factor receptor, mBC Metastatic breast cancer, OD Once-daily, mos Months, NS Not significant, PFS Progression-free survival, TTP Time to treatment progression, OS Overall survival, CI Confidence interval, IM Intramuscular, ORR Objective response rate, PIK3CA Phosphoinositide-3-kinase catalytic alpha-polypeptide, Wks Weeks, EFECT Evaluation of Faslodex versus Exemestane Clinical Trial, CONFIRM Comparison of faslodex in recurrent or metastatic breast cancer, PALOMA Palbociclib ongoing trials in the management of breast cancer, BOLERO The breast cancer trials of oral everolimus, MONARCH The Study of Abemaciclib [LY2835219] Combined With Fulvestrant in Women With Hormone Receptor Positive HER2 Negative Breast Cancer, MONALEESA Study of Efficacy and Safety of LEE011 in Postmenopausal Women With Advanced Breast Cancer
  2. aHER2 status not reported
  3. bIncluded both first- and second-line settings
  4. cPredominantly second-line setting
Back to article page

BMC Proceedings

ISSN: 1753-6561

Contact us