The POWER Trial: Personalised Dose Optimisation With Adjuvant Tamoxifen Therapy in Breast cancER

Condition(s) studied

Investigational drug(s) / intervention(s)

Individual dose of tamoxifen: Each subject starts their treatment with the standard dose 20 mg tamoxifen daily by oral intake. During visits 2 (3 months), 3 (six months) and 4 (twelve months), the investigator will either let the patient remain on 20 mg tamoxifen or individualise the dose. The investigator may change the daily tamoxifen from 20 mg per day to: a halved dose to 10 mg, or a doubled dose to 40 mg. The recommendation for oral intake of tablet(s) tamoxifen for a daily dose of 10, 20 or 40 mg is accordingly: for 10 mg: one tablet (20 mg) every two days for 20 mg: one tablet (20 mg) every day for 40 mg: two tablets (20 mg) every day.

Standard adjuvant therapy of tamoxifen: The global standard dose for everyone is 20 mg orally once per day. Each subject undergoes treatment with the standard dose 20 mg daily by oral intake of one tablet, with no possibility of dose adjustment during the trial.

Study summary

In Sweden, approximately 7000 women are diagnosed with hormone-sensitive breast cancer annually. According to international and national guidelines, most of these women are recommended anti-hormonal therapy for five to ten years to improve prognosis. Tamoxifen, one of the most widely used anti-hormonal agents globally, reduces the risk of recurrence by 40% and breast cancer mortality by 30%.

Tamoxifen is a pro-drug that undergoes hepatic metabolism to form endoxifen and other active metabolites. Variability in metabolic capacity affects therapeutic efficacy: poor metabolisers produce insufficient endoxifen and other active metabolites, risking therapeutic failure, while ultrarapid metabolisers generate excessive amounts, leading to intolerable adverse effects. Today, 30-50% of patients discontinue treatment prematurely due to severe side effects, resulting in suboptimal outcomes.

Currently, tamoxifen is uniformly prescribed at a daily dose of 20 mg, and so far, no clinical trials have tested whether individualised dosing could enhance adherence and improve survival outcomes. The primary objective is to evaluate whether individualised tamoxifen dosing reduces discontinuation rates and enhances patient outcomes in breast cancer treatment.

Eligibility

Primary outcome measure(s)

• Discontinuation of tamoxifen. — From enrollment to end of treatment at 60 months.
  The primary outcome is discontinuation of tamoxifen. This will be declared when any of the following four criteria are satisfied: * Agreement between patient and doctor that the patient will discontinue tamoxifen. * Patient notifies doctor that she has discontinued tamoxifen. * Patient-reported tamoxifen tablet intake of zero tablets for 13 consecutive weeks. * Patient refuses dose of tamoxifen as recommended per protocol by their clinician.

Trial sites (4)

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