Optimizing Extended Adjuvant Endocrine Therapy in Patients With Breast Cancer (SWE-Switch)

Region Örebro County

Status and phase: Not yet enrolling; Phase 3

Conditions: Breast Cancer

Treatments: Drug: Tamoxifen; Drug: Exemestane; Drug: Letrozole; Drug: Anastrozole

Study type: Interventional

Funder types: Other

Identifiers

NCT06223698

280050

Details and patient eligibility

About

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.

Enrollment: 3,832 estimated patients

Sex: Female

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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3,832 participants in 4 patient groups

Cohort 1: Aromatase inhibitors for 5 years

Experimental group

Description:

Cohort 1 (premenopausal at diagnosis => postmenopausal at randomization) 5-year tamoxifen => Randomized to Arm A (switching to aromatase inhibitors for 5 years).

Treatment:

Drug: Anastrozole

Drug: Letrozole

Drug: Exemestane

Cohort 1: Tamoxifen for 5 years

Active Comparator group

Description:

Cohort 1 (premenopausal at diagnosis => postmenopausal at randomization) 5-year tamoxifen => Randomized to Arm B (continuing with tamoxifen for 5 years).

Treatment:

Drug: Tamoxifen

Cohort 2: Tamoxifen for 5 years

Experimental group

Description:

Cohort 2 (postmenopausal at diagnosis) 5-year aromatase inhibitors => Randomized to Arm A (switching to tamoxifen for 5 years).

Treatment:

Drug: Tamoxifen

Cohort 2: Aromatase inhibitors for 2 years

Active Comparator group

Description:

Cohort 2 (postmenopausal at diagnosis) 5-year aromatase inhibitors => Randomized to Arm B (continuing with AI for 2 years).

Treatment:

Drug: Anastrozole

Drug: Letrozole

Drug: Exemestane