Optimizing Extended Adjuvant Endocrine Therapy in Patients With Breast Cancer

Phase 3

Not yet recruiting

• Conditions: Breast Cancer
• Interventions: Drug: Letrozole; Drug: Tamoxifen; Drug: Anastrozole; Drug: Exemestane

• Registration Number: NCT06223698
• Lead Sponsor: Region Örebro County

Brief Summary

Based on the risk of late recurrence in breast cancer patients with luminal disease with high-risk for recurrence, extended adjuvant endocrine therapy beyond 5 years is recommended as a valid treatment option. In premenopausal women at diagnosis converted to postmenopausal after the first five years of tamoxifen, two treatment strategies for extended adjuvant endocrine therapy are available, namely continuing with tamoxifen or switching to aromatase inhibitors (AI). No randomized evidence does exist and both treatment strategies are used in clinical practice. In postmenopausal women with higher recurrence risk initially treated with AI for five years, extended adjuvant therapy with additional two years of AI has shown to be as effective as additional five years of AI. However, no randomized evidence on whether a switching strategy of five-year extended tamoxifen is better compared to two-year extended AI is available. Both treatment strategies are used in clinical practice.

The primary objective of this register-based randomized trial is to investigate the overall survival between patients treated with switching strategy for extended adjuvant endocrine therapy compared to continuing with the same treatment as the initial 5 years in two different clinical scenarios:

* In premenopausal women at diagnosis who converted to postmenopausal after 5 years of tamoxifen.

* In postmenopausal women at diagnosis.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-12-29
• Study First Submitted QC: 2024-01-16
• Study First Posted: 2024-01-25
• Status Verified: 2025-01
• Last Update Submitted: 2025-04-16
• Last Update Posted: 2025-04-20
• Study Start: 2025-05-02
• Primary Completion: 2032-05-02
• Study Completion: 2035-05-02

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 3832

Inclusion Criteria

Cohort 1 (premenopausal women at diagnosis converted to postmenopausal)

1. Women who were pre- or perimenopausal at diagnosis
2. Luminal breast cancer (defined as estrogen-receptor positive >/=10%, HER2-negative disease).
3. Treated with tamoxifen for at least 80% of a 5-year period (+/- 6 months from treatment completion).
4. No clinical signs of metastasis after 5 years tamoxifen treatment.
5. cN+ breast cancer at diagnosis indicating the need for extended adjuvant endocrine therapy.
6. Postmenopausal status at study entry defined according to the National Comprehensive Cancer Network Guidelines.

Cohort 2 (postmenopausal women at breast cancer diagnosis)

1. Women who were postmenopausal at diagnosis.
2. Luminal breast cancer (defined as estrogen-receptor positive >/=10%, HER2-negative disease).
3. Treated with AI for at least 80% of a 5-year period (+/- 6 months from treatment completion).
4. No clinical signs of metastasis after 5 years AI treatment.
5. cN+ breast cancer at diagnosis indicating the need for extended adjuvant endocrine therapy.

Exclusion Criteria

Cohort 1

1. Prior invasive breast cancer diagnosis.
2. Other invasive malignancy within 5 years before or after breast cancer diagnosis
3. Non-luminal breast cancer (defined as estrogen-receptor < 10%).
4. Patients who were unable to complete at least 80% of 5-year initial treatment with tamoxifen.
5. Uncertain menopausal status (unable to evaluate menopausal status according to aforementioned definitions).
6. Recurrent or metastatic breast cancer within or after 5-year initial treatment with tamoxifen (DCIS-only is allowed at any time before or after breast cancer diagnosis).

8. Unable to give informed consent in Swedish. Cohort 2

1. Prior invasive breast cancer diagnosis.
2. Other invasive malignancy within 5 years before or after breast cancer diagnosis; non-Luminal breast cancer (defined as estrogen-receptor < 10%).
3. Patients who were unable to complete at least 80% of 5-year initial treatment with AI.
4. Recurrent or metastatic breast cancer within or after 5-year initial treatment with AI (DCIS-only is allowed at any time before or after breast cancer diagnosis).

6. No contraindication for tamoxifen therapy. 7) Unable to give informed consent in Swedish.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1: Aromatase inhibitors for 5 years	Letrozole	Cohort 1 (premenopausal at diagnosis =\> postmenopausal at randomization) 5-year tamoxifen =\> Randomized to Arm A (switching to aromatase inhibitors for 5 years).
Cohort 2: Aromatase inhibitors for 2 years	Exemestane	Cohort 2 (postmenopausal at diagnosis) 5-year aromatase inhibitors =\> Randomized to Arm B (continuing with AI for 2 years).
Cohort 1: Aromatase inhibitors for 5 years	Anastrozole	Cohort 1 (premenopausal at diagnosis =\> postmenopausal at randomization) 5-year tamoxifen =\> Randomized to Arm A (switching to aromatase inhibitors for 5 years).
Cohort 1: Aromatase inhibitors for 5 years	Exemestane	Cohort 1 (premenopausal at diagnosis =\> postmenopausal at randomization) 5-year tamoxifen =\> Randomized to Arm A (switching to aromatase inhibitors for 5 years).
Cohort 1: Tamoxifen for 5 years	Tamoxifen	Cohort 1 (premenopausal at diagnosis =\> postmenopausal at randomization) 5-year tamoxifen =\> Randomized to Arm B (continuing with tamoxifen for 5 years).
Cohort 2: Tamoxifen for 5 years	Tamoxifen	Cohort 2 (postmenopausal at diagnosis) 5-year aromatase inhibitors =\> Randomized to Arm A (switching to tamoxifen for 5 years).
Cohort 2: Aromatase inhibitors for 2 years	Letrozole	Cohort 2 (postmenopausal at diagnosis) 5-year aromatase inhibitors =\> Randomized to Arm B (continuing with AI for 2 years).
Cohort 2: Aromatase inhibitors for 2 years	Anastrozole	Cohort 2 (postmenopausal at diagnosis) 5-year aromatase inhibitors =\> Randomized to Arm B (continuing with AI for 2 years).

Primary Outcome Measures

Name	Time	Method
Overall survival	120 months

Secondary Outcome Measures

Name	Time	Method
Adherence to treatment strategies (medical possession ratio)	36 months; 60 months; 120 months	Adherence will be calculated by using medication possession ratio (MPR; the sum of the days' supply for all fills of a given drug in a particular time period, divided by the number of days in the time period). A MPR of \>/= 80% is defined as good adherence
Duration of sick leave	36 months; 60 months; 120 months
Invasive disease-free survival	36 months; 60 months; 120 months
Distant disease-free survival	36 months; 60 months; 120 months
Breast cancer-specific survival	36 months; 60 months; 120 months
Overall survival	36 months; 60 months
Frequency of selected grade 3/4 toxicities	36 months; 60 months; 120 months	Selected grade 3 or 4 toxicities that lead to hospitalization will be captured and analyzed for each study arm.
Overall quality of life (EORTC QLQC30)	24 months; 60 months	Assessment of overall quality of life through global health status from EORTC QLQC30 (scale 0 to 100; higher score indicates better overall quality of life)

Trial Locations

Locations (15)

Visby Hospital; 🇸🇪 Visby, Gotland, Sweden

Gävle Hospital; 🇸🇪 Gävle, Sweden

Kalmar Hospital; 🇸🇪 Kalmar, Sweden

St Göran Capio Hospital; 🇸🇪 Stockholm, Sweden

Växjö Hospital; 🇸🇪 Växjö, Sweden

General Hospital of Eskilstuna; 🇸🇪 Eskilstuna, Sweden

Falun County Hospital; 🇸🇪 Falun, Sweden

Sahlgrenska University Hospital; 🇸🇪 Göteborg, Sweden

Ryhov County Hospital; 🇸🇪 Jönköping, Sweden

Lund University Hospital; 🇸🇪 Lund, Sweden

Karolinska University Hospital; 🇸🇪 Stockholm, Sweden

University Hospital of Umeå; 🇸🇪 Umeå, Sweden

Akademiska University Hospital Uppsala; 🇸🇪 Uppsala, Sweden

Västerås General Hospital; 🇸🇪 Västerås, Sweden

Örebro University Hospital; 🇸🇪 Örebro, Sweden