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

Optimizing Extended Adjuvant Endocrine Therapy in Patients With Breast Cancer: a Registry-based Randomized Clinical Trial - SWE-Switch Breast Cancer Trial

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Letrozole; Drug: Anastrozole; Drug: Exemestane; Drug: Tamoxifen

• Study Type: Interventional
• Enrollment (Estimated): 3832
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Antonis Valachis, MD, PhD; Phone Number: 0046 196021000; Email: antonios.valachis@oru.se

Study Locations

• Sweden
  • Eskilstuna, Sweden
    • General Hospital of Eskilstuna
    • Contact: Andreas Nearchou, MD
  • Falun, Sweden
    • Falun county hospital
    • Contact: Maria Annerbo, MD
  • Gävle, Sweden
    • Gävle Hospital
    • Contact: Per Edlund, MD, PhD
    • Contact: Per Edlund
  • Göteborg, Sweden
    • Sahlgrenska University Hospital
    • Contact: Barbro Linderholm, MD, PhD
    • Contact: Barbro Linderholm, MD; PhD
  • Jönköping, Sweden
    • Ryhov County Hospital
    • Contact: Maria Ekholm, MD, PhD
  • Kalmar, Sweden
    • Kalmar Hospital
    • Contact: Monika Uminska, MD
  • Lund, Sweden
    • Lund University Hospital
    • Contact: Niklas Loman, MD, PhD
  • Stockholm, Sweden
    • Karolinska University Hospital
    • Contact: Theodoros Foukakis, MD, PhD
    • Contact: Alexios Matikas, MD, PhD
  • Stockholm, Sweden
    • St Göran Capio Hospital
    • Contact: Jenny Bergqvist, Md, PhD
  • Umeå, Sweden
    • University Hospital of Umeå
    • Contact: Anne Andersson, MD, PhD
  • Uppsala, Sweden
    • Akademiska University Hospital Uppsala
    • Contact: Henrik Lindman, MD, PhD
    • Contact: Henrik Lindman, PD, PhD
  • Västerås, Sweden
    • Västerås General Hospital
    • Contact: Cecilia Nilsson, MD, PhD
  • Växjö, Sweden
    • Växjö Hospital
    • Contact: Carina Bayer
    • Contact: Carina Bayer, MD
  • Örebro, Sweden
    • Orebro University Hospital
    • Contact: Antonis Valachis, MD, PhD
  • Gotland
    • Visby, Gotland, Sweden
      • Visby Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Aromatase inhibitors for 5 years; Cohort 1 (premenopausal at diagnosis => postmenopausal at randomization) 5-year tamoxifen => Randomized to Arm A (switching to aromatase inhibitors for 5 years).	Drug: Letrozole; Letrozole 2.5 mg daily; Drug: Anastrozole; Anastrozole 1 mg daily; Drug: Exemestane; Exemestane 25 mg daily
Active Comparator: Cohort 1: Tamoxifen for 5 years; Cohort 1 (premenopausal at diagnosis => postmenopausal at randomization) 5-year tamoxifen => Randomized to Arm B (continuing with tamoxifen for 5 years).	Drug: Tamoxifen; Tamoxifen 20 mg daily
Experimental: Cohort 2: Tamoxifen for 5 years; Cohort 2 (postmenopausal at diagnosis) 5-year aromatase inhibitors => Randomized to Arm A (switching to tamoxifen for 5 years).	Drug: Tamoxifen; Tamoxifen 20 mg daily
Active Comparator: Cohort 2: Aromatase inhibitors for 2 years; Cohort 2 (postmenopausal at diagnosis) 5-year aromatase inhibitors => Randomized to Arm B (continuing with AI for 2 years).	Drug: Letrozole; Letrozole 2.5 mg daily; Drug: Anastrozole; Anastrozole 1 mg daily; Drug: Exemestane; Exemestane 25 mg daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival	120 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Selected grade 3 or 4 toxicities that lead to hospitalization will be captured and analyzed for each study arm.	36 months; 60 months; 120 months
Overall quality of life (EORTC QLQC30)	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)	24 months; 60 months
Adherence to treatment strategies (medical possession ratio)	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	36 months; 60 months; 120 months
Duration of sick leave		36 months; 60 months; 120 months

Collaborators and Investigators

• Sponsor: Region Örebro County
• Collaborators: Mid-Sweden Regional Cancer Centre; Akademiska University Hospital, Uppsala, Sweden

Study record dates

Study Major Dates

• Study Start (Estimated): May 2, 2025
• Primary Completion (Estimated): May 2, 2032
• Study Completion (Estimated): May 2, 2035

Study Registration Dates

• First Submitted: December 29, 2023
• First Submitted That Met QC Criteria: January 16, 2024
• First Posted (Actual): January 25, 2024

Study Record Updates

• Last Update Posted (Actual): April 20, 2025
• Last Update Submitted That Met QC Criteria: April 16, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: breast cancer; adjuvant therapy; endocrine treatment; extended therapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Enzyme Inhibitors; Bone Density Conservation Agents; Steroid Synthesis Inhibitors; Hormone Antagonists; Estrogen Antagonists; Aromatase Inhibitors; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Letrozole; Anastrozole; Tamoxifen; Exemestane
• Other Study ID Numbers: 280050

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No