Rethinking Xofigo: Drug's Benefits Go Beyond Pain Palliation in Prostate Cancer

The radiopharmaceutical Xofigo (radium-223 dichloride) has demonstrated a median overall survival (OS) benefit of nearly three months compared with placebo for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC).

Despite the fact that it has been three years since this data from the pivotal ALSYMPCA trial was released and the drug was approved by the FDA, many oncologists still need to be educated regarding Xofigo's benefits beyond pain palliation, says Phillip J. Koo.

“Oncologists need to acknowledge the fact that this radiopharmaceutical improves survival,” says Koo, a radiologist of Memorial Hospital and University of Colorado Hospital. “Yes, there are patients who will get pain relief, but the primary endpoint of the ALSYMPCA trial was overall survival, and that is what makes this drug significant.”

CURE: What do you envision for the role of Xofigo?

In an interview with CURE at the 26th International Prostate Cancer Update (IPCU) meeting held January 20-23, 2016, in Denver, Colorado, Koo discussed the benefits of Xofigo and why he thinks it is time the use of the drug becomes more widespread for the treatment of mCRPC, and potentially other cancers.Xofigo is a game-changing therapeutic radiopharmaceutical. When it comes to unsealed sources of radiation, this is the first one that has shown an OS benefit. That has never been done with radiopharmaceuticals in the past.

Are there any challenges with Xofigo?

Why do you think that many oncologists still view it as only a palliative treatment?

There are also secondary benefits, including delaying time to first skeletal-related event. It is also the first alpha emitter that has been approved. The beauty of an alpha emitter is that it packs a more powerful punch, so it travels a shorter distance. You are actually hitting the disease harder and you are not hitting healthy cells as much, so the complication rates are decreased. Because of those reasons, Xofigo is really making a big impact.I think the biggest challenge is that oncologists still see it as a palliative tool. The message is that patients need to get all six doses. Oncologists need to figure out a way to get them all six doses, if possible. That becomes a lot easier if they are treated earlier in their disease. There are data showing that patients who have lower burden bone disease do better with Xofigo, compared with patients who are treated at the end stage of disease.I think there is this association of Xofigo as a radiopharmaceutical in the past, such as samarium 153 lexidronam. In clinical practice, those aren’t used very often because they do cause significant bone marrow suppression, which prevents oncologists from having the option of giving chemotherapy afterwards, if needed.

Do you think there is potential for Xofigo to be used in combination with other agents?

I think that is the biggest problem; it is still being put in that same type of class when it really it doesn’t belong there. This is because it’s an alpha emitter and it actually improves overall survival. ALSYMPCA data have shown that Xofigo can be given safely before or after chemotherapy.To me, this makes a lot of sense because Xofigo is very specific for bone. It targets the bone. It doesn’t target visceral disease, it doesn’t target nodal disease, and it has no known effect to the soft tissues. If you can hit the bone disease using Xofigo and hit soft-tissue disease with drugs like Zytiga (abiraterone) or Xtandi (enzalutamide) simultaneously, you will get a great effect.

If you look at the data from the University of Texas MD Anderson Cancer Center’s series that was published, it showed that use of Zytiga resulted in an improved benefit with the addition of Xofigo. These combination therapies make a lot of sense. There are no crossover side effects when the two are put together.

There are also trials that have combined Xofigo with chemotherapy. At the Genitourinary Cancers Symposium held earlier this month, there were some preliminary data that showed it was safe, although I do not believe the chemotherapy doses were at the same level as they typically are.

Do you see the use of Xofigo expanding in the future?

However, this is still promising. There is risk with Xofigo and chemotherapy because there is bone marrow suppression with those drugs, but it is an area that should be interesting to learn more about.The great thing about Xofigo is that it has a lot of potential in several diseases. We are currently focusing on prostate cancer, but there are clinical trials up and running looking at it for use in patients with breast cancer. We have a site at our own hospital — the principal investigator is Christine Fisher, who is using this in patients with breast cancer with bone metastases.

The data on that will be accumulating in the near future. I fully expect it to have similar effects in breast cancer because the mechanism of action is the same; it circulates throughout the body and it localizes the bone. Bone metastases tend to have increased surface area of the bone, so it targets those areas. Whether you are dealing with prostate cancer, breast cancer, thyroid cancer, or even sarcomas, physiologically, it makes a lot of sense.