Comparative efficacy of bisphosphonates in metastatic breast and prostate cancer and multiple myeloma: a mixed-treatment meta-analysis.

PURPOSE A mixed-treatment comparison (MTC) was undertaken to compare the efficacy of zoledronic acid, clodronate, pamidronate, and ibandronate (i.v. and oral) in patients with skeletal-related events (SRE) secondary to metastatic breast and prostate cancer and multiple myeloma. EXPERIMENTAL DESIGN Studies of bisphosphonates in the three malignancies were identified and SRE data were extracted. Outcomes from the MTC were expressed as the annual SRE rate and as the mean likelihood (probability) ratio for the rate of SREs during treatment with zoledronic acid compared with the other bisphosphonates. RESULTS A total of 17 studies were identified (7 breast, 3 prostate, and 7 multiple myeloma). Data were available for all bisphosphonates in breast cancer; no data were available for ibandronate (oral or i.v.) in prostate cancer or for oral ibandronate in multiple myeloma. The SRE rates in breast cancer were 1.60 for zoledronic acid, 1.67 for oral ibandronate (excess SRE rate, 4%), 1.70 for i.v. ibandronate (6%), 2.07 for pamidronate (29%), and 2.29 for clodronate (42%). In prostate cancer, the SRE rates were 0.83 for zoledronic acid, 1.11 for clodronate (35%), and 1.41 for pamidronate (71%). In multiple myeloma, the SRE rates were 1.43 for zoledronic acid, 1.64 for pamidronate (15%), 1.90 for clodronate (33%), and 2.49 for i.v. ibandronate (75%). CONCLUSIONS Zoledronic acid seems to be the most efficacious bisphosphonate for reducing the risk of SREs in patients with cancer of the breast or prostate and those with multiple myeloma.