Oral clodronate for adjuvant treatment of operable breast cancer (National Surgical Adjuvant Breast and Bowel Project protocol B-34): a multicentre, placebo-controlled, randomised trial
The Lancet Oncology, 06/18/2012
Paterson AHG et al. – Findings of NSABP B-34 suggest that bisphosphonates might have anticancer benefits for older postmenopausal women. A meta-analysis of adjuvant bisphosphonate trials is suggested before recommendations for use in non-osteoporotic postmenopausal women with primary breast cancer are made.Methods
- NSABP B-34 is a multicentre, randomised, double-blind, placebo-controlled study in 3323 women with stage 1—3 breast cancer.
- After surgery to remove the tumour, patients were stratified by age, axillary nodes, and oestrogen and progesterone receptor status and randomly assigned in a 1:1 ratio to either oral clodronate 1600 mg daily for 3 years (n=1662) or placebo (1661).
- The primary endpoint was disease-free survival, analysed by intention to treat.
- Median follow-up was 90·7 months (IQR 82·7—100·0) and 3311 patients had data for this period.
- Disease-free survival did not differ between groups (286 events in the clodronate group vs 312 in the placebo group; hazard ratio 0·91, 95% CI 0·78—1·07; p=0·27).
- Moreover, no differences were recorded for overall survival (0·84, 0·67—1·05; p=0·13), recurrence-free interval (0·83, 0·67—1·04; p=0·10), or bone metastasis-free interval (0·77, 0·55—1·07; p=0·12).
- Non-bone metastasis-free interval was slightly increased with clodronate (0·74, 0·55—1·00; p=0·047).
- Analyses in women age 50 years or older on study entry showed benefits of clodronate for recurrence-free interval (0·75, 0·57—0·99; p=0·045), bone metastasis-free interval (0·62, 0·40—0·95; p=0·027), and non-bone metastasis-free interval (0·63, 0·43—0·91; p=0·014), but not for overall survival (0·80, 0·61—1·04, p=0·094).
- Adherence to treatment at 3 years was 56% for the clodronate group and 60% for the placebo group.
- Grade 3 or higher liver dysfunction was noted in 23 of 1612 patients in the clodronate group and 12 of 1623 patients in the placebo group; grade 3—4 diarrhoea was noted in 28 patients in the clodronate group and in ten in the placebo group.
- There was one possible case of osteonecrosis of the jaw in the clodronate group.