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An Emerging Potential Therapy for Bone Health: Denosumab

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In my last post, we covered an introduction to bone metastases and the use of the class of drugs known as bisphosphonates as a current standard treatment. A new investigational approach is also being tested, known as denosumab (AMG-162), which is a different from the bisphosphonates. A monoclonal antibody, denosumab is designed to attach to and inhibit an activating factor in the blood (termed a ligand) that stimulates the function of osteoclasts (the cells breaking down bone), thus providing a novel way of decreasing bone resorption. The ligand in this instance is called RANKL (which stands for Receptor Activator of Nuclear Factor-KappaBeta Ligand).

Denosumabandimmunity

(Click to enlarge)

The early research in this field was in the treatment of osteoporosis. Denosumab is given as a subcutaneous injection (under the skin), and different studies have used different time intervals between injections: 1 month, 3 months, or 6 months.

In the only published large randomized trial, women with resected breast cancer who were receiving adjuvant endocrine therapy were given either denosumab every 6 months or placebo. The goal of this study was assessing skeletel-related events (SREs), but instead was the relative change in bone density over time. This trial demonstrated that Denosumab increased bone density compared with placebo. It is not clear, however, whether this equals a reduced risk of bone fracture, or whether this would translate into a reduced risk for SREs.

The most common side effects of denosumab included joint pains, body aches, and fatigue. The rates of the side effects were similar though between patients who received denosumab and placebo. Currently there are a number of ongoing clinical trials with denosumab.

Though most are for osteoporosis, there is also active research for prostate cancer, breast cancer, and a study in advanced cancers that excludes breast and prostate cancer (26 total trials currently listed on www.clinicaltrials.gov).

In the initial trial, it would appear that denosumab may have fewer side effects than the bisphosphonates, though more trials really need to be done before this can be understood. Not enough evidence is available yet for us to see whether denusomab may also cause osteonecrosis of the jaw (ONJ), for example.

So what do we do with this information? SREs don’t happen in every patient with bone metastases, but clearly SREs are something we want to prevent in any patient. When a cancer is not curable, quality of life is of the utmost importance. Prevention of SREs helps keep quality of life good, as long as the prevention does not itself hamper quality of life. As with other cancer therapies, if we could predict which patients have the best chance of responding to a drug, or which patients have the highest chance of developing toxicities, we might be able to more specifically tailor therapy for better outcomes.

Currently Zometa (zoledronate) and Aredia (pamidronate) are the standard of care therapies for prevention of SREs for patients with metastatic cancer. Whether or not to use these drugs in each individual patient requires careful evaluation of the individual risks and benefits. Denosumab is an interesting drug, but will require more study before it would become widely available. There are many questions that have been raised recently, from questions about possible survival differences with Zometa to better tolerability with denosumab. We just don’t know the answers to those questions yet.


5 Responses to An Emerging Potential Therapy for Bone Health: Denosumab

  • Kathie says:

    Thanks, Dr. Sanborn. I printed out your article and will take it with me to my next onc. visit. My diagnosis is Stage IV NSCLC and I’m having an excellent result with Tarceva. It is the only cancer treatment I have/or ever have recieved. I am currently taking Zometa every four weeks due to bone lesions.

  • Dr Sanborn says:

    Hello Kathie–

    Thank you, I am glad you found the information helpful. This is a challenging issue without easy answers.

  • Apra says:

    I would like to know the availability of denosumab in America. Is it widely available? Is is still very expensive?
    Thank you
    Apra

  • Dr West
    Dr West says:

    It’s about twice as expensive as Zometa, but it’s pretty widely available at this point in the US.

  • Apra says:

    Dr. West, Thank you for prompt reply once again.
    My onc refuses to prescribe denosumab for my husband saying it is not significantly different from Zometa. I would like it because I have seen from this site that it is kinder on the kidneys.
    Apra

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