SAN ANTONIO — Monthly denosumab may prove to suppress bone turnover when patients with cancer metastatic to bone do not respond adequately to bisphosphonate therapy, Dr. Allan Lipton said at the Sixth International Meeting on Cancer-Induced Bone Disease.
The drug is a fully human monoclonal antibody to RANK ligand, inhibiting the differentiation and proliferation of osteoclasts, and thus reducing bone turnover. It also is being investigated for the treatment of postmenopausal osteoporosis.
Dr. Lipton presented the interim results of a phase II study in patients in whom zoledronic acid or pamidronate failed to adequately suppress urinary markers of bone turnover.
Adequate suppression is important in these patients not only because it helps prevent fractures, but because it delays tumor progression and improves survival.
The interim analysis included 49 patients who have finished the 25-week trial. Eventually the study will enroll 135 patients.
Of initial patients, 40% had metastatic breast cancer, 40% had metastatic prostate cancer, 10% had multiple myeloma, and the rest had other solid tumors. Most (80%) had been on zoledronic acid; the rest had been on pamidronate. All patients still had urinary N-telopeptide (NTx) levels of more than 50 nmol/mmol creatinine.
Overall, more patients on denosumab than on bisphosphonates experienced a decrease in their urinary NTx levels to less than 50 nmol/mmol creatinine (76% vs. 38%). The difference was still significant when the groups were divided according to baseline NTx levels.
Among those who started with a level of 51–100 nmol/mmol creatinine, 87% of those on denosumab achieved the target compared with 50% of those taking bisphosphonates.
Among those with baseline levels of more than 100 nmol/mmol creatinine, two-thirds of the denosumab group achieved the goal compared with 25% of the bisphosphonate group.
Those who received denosumab every 4 weeks had the longest duration of adequate suppression (a mean of 140 days), followed by patients taking the drug every 12 weeks. Bisphosphonate-treated patients maintained adequate suppression for a mean of 30 days.
The meeting was sponsored by the Cancer and Bone Society. The study was sponsored by Amgen Inc. Dr. Lipton, of the Penn State Milton S. Hershey Medical Center, Hershey, Pa., is a consultant for the company.