Hedgehog Agents Making an Impact in Treatment of Basal Cell Carcinoma

Therapeutic options have been severely limited for patients with locally advanced or unresectable basal cell carcinoma.

Morganna Freeman, DO

Therapeutic options have been severely limited for patients with locally advanced or unresectable basal cell carcinoma, according to Morganna Freeman, DO, chief oncology fellow at Moffitt Cancer Center.

“When basal cells grow beyond the skin, it metastasizes—which is rare, but can happen,” says Freeman. “A few years ago, it was discovered that there was a certain protein that was essential to basal cell growth called a hedgehog protein,” says Freeman. “Now, we have 2 FDA-approved hedgehog inhibitors—vismodegib (Erivedge) and sonidegib (Odomzo)—which target this protein and can kill basal cells successfully.”

In an interview withTargeted Oncology, Freeman explains the impact of hedgehog inhibitors in basal cell carcinoma, the ideal patient to receive them, and emerging agents on the horizon for treatment of the disease.

TARGETED ONCOLOGY:What impact have hedgehog inhibitors had for patients with locally advanced or unresectable basal cell carcinoma?

Freeman:It is not like chemotherapy, which patients are committed to. Based on the data that we have seen with both of those drugs, these rare patients who develop metastatic disease or even unresectable disease that is confined to the skin, can get a long-lasting clinical benefit with a very tolerable side effect profile. The most common side effects that we see with these agents are muscle cramps and fatigue but, otherwise, it is very well tolerated.

TARGETED ONCOLOGY:Who is the optimal patient to receive hedgehog inhibitors?

Metastatic basal cell carcinoma is fairly rare. If I am seeing a patient who has a number of basal cell growths and the surgeon thinks it would be too extensive of a surgery to perform then, obviously, these hedgehog inhibitors have a role.

If it is a patient with metastatic basal cell carcinoma, a lot depends on the burden of metastatic disease. Some patients have a few spots in the bone that are asymptomatic and, if they are slowly growing, then we may just decide to watch them.

However, if they have metastases that are large, symptomatic, or growing quickly, then we would definitely think about putting them on hedgehog inhibitors at that point. We do know that once the patient stops therapy, the basal cell will regrow.

Therefore, patients should expect that this would be a chronic, long-term treatment in order to keep their disease in remission. A lot of discussions I have with patients are on the risks and benefits regarding when we should initiate therapy and for how long, and what we would do if the cancer should end up recurring or relapsing in a different place.

TARGETED ONCOLOGY:Are there other emerging agents or treatment strategies being explored for basal cell carcinoma?

One of the things we are learning is, in addition to having the hedgehog pathway necessary for growth, it also depends on VEGF—which is another important protein in cancer. VEGF is essentially what enables cancer to grow blood vessels toward itself, and allows it to continue to grow and metastasize.

There have been some interesting data that would suggest that targeting VEGF, or other growth pathways using TKIs, might be an emerging way to treat basal cell carcinoma even more effectively.

TARGETED ONCOLOGY:What are the treatment options for patients with early-stage basal cell carcinoma?

Right now, for patients who have early-stage basal cell carcinoma, our standard approach is surgery. The problem is that basal cells tend to recur; they can recur at the site of surgical incision or in other places, as well. Educating patients about sun exposure and protecting themselves from the sun after a basal cell carcinoma has occurred can be helpful, and is certainly the most preventative action that can be taken.