A randomized, double-blind, phase II, exploratory trial evaluating the palliative benefit of either continuing pamidronate or switching to zoledronic acid in patients with high-risk bone metastases from breast cancer

• Published in: Breast cancer research and treatment Vol. 155; no. 1; pp. 77 - 84
• Main Authors: Jacobs, C., Kuchuk, I., Bouganim, N., Smith, S., Mazzarello, S., Vandermeer, L., Dranitsaris, G., Dent, S., Gertler, S., Verma, S., Song, X., Simos, S., Cella, D., Clemons, M.
• Format: Journal Article
• Language: English
• Published: New York Springer US 2016; Springer; Springer Nature B.V
• Subjects: Adult; Aged; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Bone cancer; Bone Density Conservation Agents - administration & dosage; Bone Density Conservation Agents - adverse effects; Bone Density Conservation Agents - therapeutic use; Bone disorder agents; Bone Neoplasms - drug therapy; Bone Neoplasms - secondary; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cancer metastasis; Cancer patients; Cancer research; Cancer therapies; Care and treatment; Chemotherapy; Clinical Trial; Clinical trials; Combined Modality Therapy; Complications and side effects; Diphosphonates - administration & dosage; Diphosphonates - adverse effects; Diphosphonates - therapeutic use; Drug Substitution; Female; Humans; Imidazoles - administration & dosage; Imidazoles - adverse effects; Imidazoles - therapeutic use; Medicine; Medicine & Public Health; Metastasis; Middle Aged; Oncology; Palliative Care; Quality of Life; Treatment Outcome; Zoledronic acid; Pamidronate; Bisphosphonate; Bone metastasis; Breast cancer
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-015-3646-2

Previous studies suggest switching from pamidronate to a more potent bone-targeted agent is associated with biomarker and palliative response in breast cancer patients with bone metastases. Until now, this has not been addressed in a double-blind, randomized trial. Breast cancer patients with high-risk bone metastases, despite >3 months of pamidronate, were randomized to either continue pamidronate or switch to zoledronic acid every 4 weeks for 12 weeks. Primary outcome was the proportion of patients achieving a fall in serum C-telopeptide (sCTx) at 12 weeks. Secondary outcomes included difference in mean sCTx, pain scores, quality of life, toxicity, and skeletal-related events (SREs). Seventy-three patients entered the study; median age 61 years (range 37–87). Proportion of patients achieving a fall in sCTx over the 12-week evaluation period was 26/32 (81 %) with zoledronic acid and 18/29 (62 %) with pamidronate ( p  = 0.095). Mean decrease in sCTx (mean difference between groups = 50 ng/L, 95 % CI 18–84; p  = 0.003) was significantly greater in patients who received zoledronic acid. Quality of life, pain scores, toxicity, and frequency of new SREs were comparable between the two arms. While a switch from pamidronate to zoledronic acid resulted in reduction in mean sCTx, there were no significant differences between the arms for proportion of patients achieving a reduction in sCTx, quality of life, pain scores, toxicity or SREs. Given the lack of palliative improvement, the current data do not support a switching strategy.