Sonidegib Approved for Advanced Basal Cell Carcinoma

Oncologists now have a new tool for treating locally advanced basal cell carcinoma. On July 24, 2015, The US Food and Drug Administration (FDA) approved sonidegib (Odomzo) to treat patients with this type of cancer after it has recurred following surgery or radiation therapy. Sonidegib has also been approved for patients with locally advanced basal cell carcinoma who are not candidates for surgery or radiation therapy.

Sonidegib is a given orally once a day and it works by inhibiting the Hedgehog pathway, which is active in basal cell cancers. This agent may offer new hope for many patients who until now have had very few treatment options. Skin cancer is the most common cancer in the United States and basal cell carcinoma accounts for approximately 80% of nonmelanoma skin cancers.

“Our increasing understanding of molecular pathways involved in cancer has led to approvals of many oncology drugs in difficult-to-treat diseases for which few therapeutic options previously existed,” said Richard Pazdur, MD, who is the director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, Bethesda, Maryland. “Thanks to a better understanding of the Hedgehog pathway, the FDA has now approved two drugs for the treatment of basal cell carcinoma just in the last three years.” In 2012, vismodegib (Erivedge) was the first drug approved to treat locally advanced and metastatic basal cell carcinoma. 

The efficacy of sonidegib was established in a multicenter, double-blind clinical trial, in which 66 patients with locally advanced basal cell carcinoma were randomly assigned to receive sonidegib 200 mg daily and 128 patients were assigned to receive sonidegib 800 mg daily. The study’s primary endpoint was objective response rate, and the results showed that 58% of patients treated with sonidegib 200 mg had their tumors shrink or disappear. This effect lasted at least 1.9 to 18.6 months, and approximately 50% of the responding patients’ tumor shrinkage lasted 6 months or longer. Response rates were similar in patients who received 800 mg daily dose; however, side effects were more common at this dose.

At a dose of 200 mg daily, the most common side effects of sonidegib were muscle spasms, alopecia, dysgeusia, fatigue, nausea, musculoskeletal pain, diarrhea, decreased weight, decreased appetite, myalgia, abdominal pain, headache, pain, vomiting, and pruritus. This treatment also has the potential to cause serious musculoskeletal-related side effects, including increased serum creatine kinase levels (with rare reports of rhabdomyolysis), muscle spasms, and myalgia.

Sonidegib also carries a Boxed Warning alerting clinicians that it may cause death or severe birth defects in a developing fetus when administered to a pregnant woman. Pregnancy status should be verified by clinicians prior to the start of sonidegib treatment, and both male and female patients should be warned about these risks and advised to use effective contraception.