Introduction
Methods
Efficacy of treatment up to 5 years
Efficacy of extended treatment duration
Extended tamoxifen monotherapy
Extended sequential regimen
Compliance
Tolerability
Postmenopausal due to prior chemotherapy
Future perspectives
Study acronym Trial ID number Phase country | Sample size (n) | Purpose | Inclusion criteria | Endocrine therapy before randomization (years) | Treatment arms | Outcome measures | First results expected |
---|---|---|---|---|---|---|---|
Duration endocrine treatment | |||||||
GIM-4-LEAD NCT01064635 Phase III Italy | 4050 | Comparing the efficacy of different regimens of L in postmenopausal women with stage I, II, or III BC previously treated with T | Postmenopausal women with HR+ BC stage I–III. Any nodal stage. No metastases. Completed initial T treatment. | 2–3 years T | 1) 2–3 years L 2) 5 years L | OS Safety | 2015 |
ABCSG 16 SALSA NCT00295620 Phase III Austria | 3486 | Efficacy of a further 2 years vs. a further 5 years of adjuvant treatment with A after initial 5 years of adjuvant endocrine therapy | Postmenopausal women with HR+ BC Any nodal stage No metastases Completed initial anti-hormonal treatment | 5 years of any endocrine therapy | 1) 2 years A 2) 5 years A | DFS OS Fracture occurrence Secondary carcinoma Contralateral BC | 2019 |
SOLE/ABCSG 35–07 NCT00553410 Phase III International | 4800 | Continuous L versus intermittent L in postmenopausal women with BC who received 4–6 years of endocrine therapy | Postmenopausal women with HR+ BC Any nodal stage No metastases Completed initial endocrine treatment < 12 months ago | 4–6 years of any endocrine therapy | 1) 5 years L continuously 2) 5 years intermittent L (4 × 9 months, 1 × 12 months) | DFS OS Distant DFS BC free interval Second malignancies Deaths without prior cancer events Adverse events | 2021 |
MINDACT NCT00433589 Phase III International | 6589 | Comparing the efficacy of 7 years of L with 2 years of T followed by 5 years of L | Postmenopausal women with HR+ BC 0–3 positive lymph nodes No metastases | none | 1) 7 years L 2) 2 years T – 5 years L | DFS OS Safety | Unknown |
N-SAS-BC-05 JPRN-UMIN000000818 | 2500 | Comparing the efficacy of 5 year A after either 5 years of A or 5 years of sequential therapy with T followed by A | Postmenopausal women with HR+ BC Any nodal stage No metastases | 5 years of A or 5 years of sequential therapy (T followed by A) | 1) 5 years A 2) no additional endocrine treatment | DFS OS DDFS Adverse events QALY HRQOL | Unknown |
Sequenced treatment versus monotherapy | |||||||
GIM-3-FATA NCT00541086 Phase III Italy | 10,000 | Evaluate the efficacy of sequenced treatment versus AI monotherapy | Postmenopausal women with HR+ BC, stage I–III Any nodal stage No metastases Completed initial endocrine treatment < 2 years ago | none | 1) 5 years A, E, or L monotherapy 2) 2.5 years T – 2.5 years A, E, or L | DFS OS DDFS Contralateral BC BC free interval Second malignancy Effects on lipid profile Toxicity | 2018 |
Sequential or concurrent with chemotherapy | |||||||
GIM-10-CONSENT NCT02918084 Phase III | 1000 | Concurrent versus sequential AI for a total of 5 years in postmenopausal patients receiving adjuvant chemotherapy for BC | Postmenopausal women with HR+ BC Any lymph node status No metastases | none | 1) Adjuvant chemotherapy followed by 5 years AI (sequential) 2) Adjuvant chemotherapy and 5 years AI concurrent | DFS OS Genomic analysis | 2028 |
Comparison of aromatase inhibitors | |||||||
FACE NCT00248170 Phase III International | 4160 | 5 years of adjuvant L versus A in postmenopausal women with HR-positive, node positive BC | Postmenopausal women with HR+ BC Positive lymph nodes No metastases Recently underwent surgery | none | 1) 5 years A 2) 5 years L | DFS Safety OS DDFS Cancer-specific survival Effect on lipid profile Bone fractures | 2018 |
PHACS NCT01127295 Phase IV France | 2000 | The correlation between pharmacokinetic and pharmacogenetic parameters of adjuvant endocrine BC treatment, during the first 3 years | Postmenopausal women with HR+ BC Any lymph node status No metastases | none | 1) 5 years T 2) 5 years L 3) 5 years A 4) 5 years E | Correlation pharmacokinetic and pharmacogenetic parameters. Relation plasmatic concentrations, effectivity and adverse events. Relation Polymorphisms and relapses. | 2019 |
Predictive factors | |||||||
PreFace NCT01908556 Phase IV Germany | 3545 | Identification of biomarkers that could predict the efficacy of adjuvant L treatment | Postmenopausal women with HR+ BC Any lymph node status No metastases | None | 1) 5 years L | DFS OS Prediction of the above by different pharmacogenetic markers on efficacy and side effects | 2015 |
Long-term follow-up | |||||||
LATTE NCT01745289 Phase III USA | 6000 | Evaluate the long-term effects of A (5 years) versus T (5 years) (follow-up ATAC trial) | All women that were included In the ATAC trial which investigated the efficacy of 5 years of A versus T. | 5 years A or 5 years T | Follow-up | Long-term RFS | 2018 |
Targeted therapy | |||||||
S1207 NCT01674140 Phase III USA | 1900 | Evaluate adjuvant endocrine therapy with or without 1 year of everolimus in patients with high risk, hormone receptor-positive, and HER2/Neu negative BC | Pre- and postmenopausal women with HR+ BC Her2– N+ | None | Any endocrine therapy combined with 1) 1 year everolimus 2) 1 year placebo | IDFS DFS OS Toxicity | 2022 |
UNIRAD NCT01805271 Phase III France | 1984 | Evaluate the safety and benefit of adding everolimus to adjuvant endocrine therapy of early BC | Pre- and postmenopausal women with HR+ BC Her2– N+ | 1 year of any endocrine therapy | 1) 1 year everolimus 2) 1 year placebo | DFS OS EFS DMFS Secondary cancer | 2021 |
EarLEE-1 NCT03078751 Phase III USA | 2000 | Evaluate efficacy and safety of ribociclib with endocrine therapy as adjuvant treatment of high-risk early BC | Pre- and postmenopausal women with HR+ BC Her2– AJCC prognostic stage group III | None | Any endocrine therapy combined with 1) 2 years ribociclib 2) 2 years placebo | IDFS RFS OS Qol | 2023 |
EarLEE-2 NCT03081234 Phase III USA | 4000 | Evaluate efficacy and safety of ribociclib with endocrine therapy as adjuvant treatment of intermediate risk early BC | Pre- and postmenopausal women with HR+ BC Her2– AJCC prognostic stage group II | None | Any endocrine therapy combined with 1) 2 years ribociclib 2) 2 years placebo | IDFS RFS OS Qol | 2025 |
MonarchE | 3580 | Evaluate efficacy of abemaciclib combined with standard adjuvant endocrine therapy versus standard adjuvant endocrine therapy alone | Pre- and postmenopausal women with HR+ BC Her2 – N+ status and 1 of the following indicating a higher risk of relapse: - 4 or more N+ - Tumor size ≥ 5 cm - Grade 3 histology - Ki67 index of ≥ 20% | None | Standard 5-year adjuvant endocrine treatment with 1) 2 years palbociclib 2) none | IDFS DRFS OS Toxicity | 2022 |
PALLAS NCT02513394 Phase III USA | 4600 | Evaluate efficacy of palbociclib with standard adjuvant endocrine therapy versus standard adjuvant endocrine therapy alone | Pre- and postmenopausal women with HR+ BC stage II or III Her2- | None | Standard 5 year adjuvant endocrine treatment with 1) 2 years palbociclib 2) none | IDFS DRFS OS LRRFS | 2020 |