Xgeva off-label and for prostate cancer

Xgeva(denosumab) is FDA indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors. In the pivotal study, denosumab was superior to zoledronic acid in delaying or preventing skeletal related events(SRE), which are essentially fractures, in patients with breast cancer metastatic to bone and was generally well tolerated. With the convenience of a under the skin injection and no requirement for monitoring kidney function, denosumab represents a potential treatment option for patients with bone metastases. It is also FDA approved for osteoporosis under the name Prolia. This drug is not FDA indicated (on label) for myeloma but is used for it and is then called off-label.

There is no legal obligation for doctors to use drugs on label. On the other hand, one should not automatically assume that this drug can be used in any cancer, whether FDA indicated or not. The thirteen member Oncologic Drugs Advisory Committee(ODAC), reviewed a study funded by the manufacturer, Amgen on 1,435 patients with castration-resistant prostate cancer. They found that the drug did prevent metastasis for the excess of four months over placebo (29 months vs 25 months). However, Xgeva did not increase expected lifespan, and the side effects were severe and judged to be too common for routine use. A measurement of the drug’s effectiveness known as bone metastasis free survival (BMFS) was increased, but this was offset by the increase in serious reportable events (SRE) the worst classification of side effects. Side effects were notable for including a form of bone destruction called osteonecrosis of the jaw in 33 (4.6 percent) of the patients treated with Xgeva. Other side effects included hypocalcemia, rashes and several types of infections. Based on this, ODAC did not recommend FDA approval for prostate cancer and the FDA did not include prostate cancer as an indication. It is not known whether there is something specific about breast cancer that led to this results or whether this was really an aberration and Xgeva is as usefull impressive cancer as this in other solid tumors cancers with bone metastasis.

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