Roger von Moos, MD, presented results of the randomized, phase 3, non-inferiority SAKK 96/12 REDUSE study (NCT02051218; Abstract 1004) evaluating the prevalence of symptomatic skeletal events (SSE) in patients with metastatic breast cancer (mBC) or metastatic castration-resistant prostate cancer (mCRPC) treated with denosumab dose-reduced to every 12 weeks (Q12w) from the standard every 4 weeks (Q4w).
Patients (N=1380) with mBC (57%) or mCRPC and at least 3 bone lesions (57% with >10) were randomly assigned to denosumab 120 mg Q4w (n=686) or to denosumab maintenance 120 mg Q12w after and induction phase of 4 doses Q4w (n=688). Patients were required to take 500 mg calcium and 400 IU vitamin D daily
At a median follow-up of 37 months, the Q4w arm received about twice the cumulative dose as the Q12w arm. The primary endpoint of time to first SSE was 56.6 months for Q4w and 56.5 months for Q12w (HR 1.023), meeting the non-inferiority endpoint. There was also no difference between arms for the secondary endpoint of time to first and subsequent SSE (HR 1.043).
In the Q12w arm risk of time to first occurrence of hypocalcemia was reduced 30% (HR 0.701); risk of time to first occurrence of ONJ/tooth infection was reduced by 25%. Overall survival was equal in both arms (43.8 months for Q4w and 40.6 months for Q12w).
A cost analysis showed a saving of 53.4% per patient with the lower dose. With 4,000-5,000 patients in Switzerland with both diseases, annual medication savings would be 15 million Swiss francs or about $90 million.
Dr. von Moos concluded denosumab Q12w after induction phase is the new international standard treatment for patients with bone metastases from BC or CRPC.
Andrea De Censi, MD, presented results of the effects of 2-5 years of low-dose tamoxifen vs placebo on BC-free interval (BCFI) by menopausal status and site of event (Abstract 10515). Standard-dose tamoxifen (20 mg/day) reduces BC recurrence and contralateral BC after ductal carcinoma in situ (DCIS), but is poorly tolerated. Low-dose tamoxifen (5 mg/day or 10 mg every other day) is effective and better tolerated, but long-term data by menopausal status are lacking.
This study (NCT06982313) analyzed individual participant data (N=1545) of 3 studies (2 random controlled trials: 007, Tam01 and 1 prospective cohort study) for the long-term effect on
Low-dose tamoxifen improved 10-year BCFI by 30% (HR=0.71). In premenopausal women, BCFI was not significantly reduced by low-dose tamoxifen, nor was ipsilateral BC. However, contralateral BC (CBC) was significantly reduced (HR 0.45 P<.01).
In postmenopausal women, BCFI was significantly reduced by low-dose tamoxifen (HR 0.51, P<.001). Ipsilateral BC was also reduced (HR 0.41 P<.001). The risk for CBC was low and not further reduced by low-dose tamoxifen. There was no increase in serious adverse events.
Dr. De Censi recommends low-dose tamoxifen for reducing ipsilateral events in postmenopausal but not premenopausal women, noting that the 55% reduction in contralateral events in premenopause warrants a clinical trial.
Results were published in the Journal of Clinical Oncology (DOI: 10.1200/JCO-26-00841) simultaneously with the presentation.
Dr. Lederman has no conflicts of interest to report.
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