Optimizing Extended Adjuvant Endocrine Therapy in Patients With Breast Cancer

Official title

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

Overview

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.

Interventions

• Drug Letrozole
  Letrozole 2.5 mg daily
• Drug Anastrozole
  Anastrozole 1 mg daily
• Drug Exemestane
  Exemestane 25 mg daily
• Drug Tamoxifen
  Tamoxifen 20 mg daily

Primary outcome measures

• Overall survival [Time frame: 120 months]

Secondary outcome measures (8)

• Invasive disease-free survival [Time frame: 36 months; 60 months; 120 months]
• Distant disease-free survival [Time frame: 36 months; 60 months; 120 months]
• Breast cancer-specific survival [Time frame: 36 months; 60 months; 120 months]
• Overall survival [Time frame: 36 months; 60 months]
• Frequency of selected grade 3/4 toxicities [Time frame: 36 months; 60 months; 120 months]
• Overall quality of life (EORTC QLQC30) [Time frame: 24 months; 60 months]
• Adherence to treatment strategies (medical possession ratio) [Time frame: 36 months; 60 months; 120 months]
• Duration of sick leave [Time frame: 36 months; 60 months; 120 months]

Eligibility criteria

Inclusion criteria

Cohort 1 (premenopausal women at diagnosis converted to postmenopausal)

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

Cohort 2 (postmenopausal women at breast cancer diagnosis)

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

Exclusion criteria

Cohort 1

• Prior invasive breast cancer diagnosis.
• Other invasive malignancy within 5 years before or after breast cancer diagnosis
• Non-luminal breast cancer (defined as estrogen-receptor < 10%).
• Patients who were unable to complete at least 80% of 5-year initial treatment with tamoxifen.
• Uncertain menopausal status (unable to evaluate menopausal status according to aforementioned definitions).
• 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

• Prior invasive breast cancer diagnosis.
• Other invasive malignancy within 5 years before or after breast cancer diagnosis; non-Luminal breast cancer (defined as estrogen-receptor < 10%).
• Patients who were unable to complete at least 80% of 5-year initial treatment with AI.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Sweden · 15 centers

• Visby Hospital — Visby
• General Hospital of Eskilstuna — Eskilstuna
• Falun County Hospital — Falun
• Gävle Hospital — Gävle
• Sahlgrenska University Hospital — Gothenburg
• Ryhov County Hospital — Jönköping
• Kalmar Hospital — Kalmar
• Lund University Hospital — Lund
• … and 7 more centers

Identifiers

NCT: NCT06223698 · 280050

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗