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FDA Approves Denosumab for Multiple Myeloma

Jason M. Broderick @jasoncology
Published: Friday, Jan 05, 2018

The FDA has approved denosumab (Xgeva) for the prevention of skeletal-related events (SREs) in patients with multiple myeloma, according to Amgen, the developer of the RANK ligand inhibitor.

Adverse events (AEs) in the study were consistent with the known safety profile for denosumab. The most common AEs in the denosumab arm were diarrhea (33.5% vs 32.4% with zoledronic acid) and nausea (31.5% vs 30.4%).

Zoledronic acid has been a standard of care for patients with multiple myeloma for the prevention of SREs, since it was approved in 2002. In a 1018-patient study,1 zoledronic acid reduced the risk of death by 22% and SREs by 25% compared with the bisphosphonate pamidronate in multiple myeloma. The median OS with zoledronic acid was 32.4 months compared with 23.4 months with pamidronate (HR, 0.78; 95% CI, 0.67-0.92).

In addition to other approvals, denosumab is currently indicated for the prevention of SREs in patients with bone metastases from a solid tumor, based upon 3 large studies comparing the agent with zoledronic acid in 5723 patients.2 Across these trials, the median time to first SRE was 27.7 months with denosumab compared with 19.5 months with zoledronic acid (HR, 0.83; 95% CI, 0.76-0.90; P <.001).

In the 3 trials, which used similar dosing schemes as the 482 study, the most common AEs were fatigue/asthenia, hypophosphatemia, and nausea. The most common AEs leading to discontinuation were osteonecrosis and hypocalcemia. Severe hypocalcemia, when vitamin D supplementation was utilized, was experienced by 3% of those treated with denosumab versus 1.4% with zoledronic acid. When supplements were not used, these rates were 3.9% and 1.0%, for denosumab and zoledronic acid, respectively.

Across the studies, renal-related dose adjustments or pauses were not required for patients taking denosumab. Eighteen percent of those in the zoledronic acid arm required a dose adjustment based on baseline CRCL levels. Once treatment had started, dosing pauses due to serum creatinine levels were required for 10% of patients in the zoledronic acid arm.

"Bone complications can be devastating for patients with multiple myeloma. Previously, treatment options for the prevention of bone complications were limited to bisphosphonates, which unlike Xgeva, are cleared by the kidneys," David M. Reese, MD, senior vice president of Translational Sciences and Oncology at Amgen, said in a press release. "We are pleased that the FDA has approved the expanded indication for Xgeva, providing a new option for patients and physicians, underscoring our commitment to advancing care for patients with multiple myeloma."

References

  1. Sanfilippo KM, Gage B, Luo S, et al. Comparative effectiveness on survival of zoledronic acid versus pamidronate in multiple myeloma. Leuk Lymphoma. 2015;56(3):615-621.
  2. Lipton A, Fizazi K, Stopeck AT, et al. Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: a combined analysis of 3 pivotal, randomised, phase 3 trials. Eur J Cancer. 2012;48:3082-3092.

 



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