By Laura Cowen
Older patients with breast cancer may benefit from adjuvant treatment with oral bisphosphonates, but further studies are needed before general application in the breast cancer population, say researchers.
The final results of the National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol B-34, published in The Lancet Oncology, show that women aged 50 years and older who received clodronate 1600 mg daily for 3 years had a significantly longer recurrence-free interval (hazard ratio [HR]=0.75), bone metastasis-free interval (HR=0.62), and nonbone metastasis-free interval (HR=0.63) than patients who received placebo.
There was no significant improvement in overall survival (HR=0.80), however, and women younger than 50 years of age appeared to derive no benefit from clodronate treatment.
Alexander Paterson (Tom Baker Cancer Centre, Calgary, Alberta, Canada) and colleagues explain that NSABP B-34 ascertained whether oral clodronate, a bisphosphonate that targets the bone microenvironment, could improve outcomes in women with stage 1‑3 breast cancer.
A total of 3323 women took part in the multicenter, randomized, double-blind study. Two-thirds of patients were older than 50 years (and thus likely to be postmenopausal), and three-quarters had negative axillary nodes and were estrogen receptor-positive.
The researchers report that overall, disease-free survival ‑ the primary endpoint ‑ did not differ significantly between the two treatment groups, with 286 events reported in the clodronate group versus 312 in the placebo group (HR=0.91).
Similarly, no significant differences were recorded for overall survival (HR=0.84), recurrence-free interval (HR=0.83), or bone metastasis-free interval (HR=0.77), but nonbone metastasis-free interval was slightly improved with clodronate (HR=0.74).
The researchers note that adherence to treatment at 3 years was 56% for the clodronate group and 60% for the placebo group, which they say is "less than optimum," and has weakened their ability to determine the overall effect of clodronate.
Few side effects were reported during follow up. Grade 3 diarrhea was more common with clodronate than with placebo (28 vs 10 events), but toxic effects, particularly osteonecrosis of the jaw and renal complications, were very low. Prevalence of second primary malignant disease was similar in both groups (114 vs 119 events for clodronate vs placebo).
In an accompanying comment, Peter Dubsky and Rupert Bartsch from the University of Vienna in Austria say: "At this stage of clinical research, bisphosphonates should not be prescribed for an assumed benefit in adjuvant management of breast cancer."
They agree with the conclusions of Paterson et al that a meta-analysis of adjuvant bisphosphonate trials is needed before any recommendations are made.
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