Oncology Overview: Sonidegib (Odomzo) for Locally Advanced Basal Cell Carcinoma

Sonidegib (Odomzo) treats adult patients with locally advanced basal cell carcinoma (BCC) that has recurred following surgery or radiation therapy.¹ Patients may also take it if they are not candidates for surgery or radiation therapy for their BCC.

BCC is the most common form of skin cancer and among the most diagnosed forms of cancer in the United States. Until recently, visomodegib was the only targeted treatment available for locally advanced BCC where surgery and radiotherapy are inappropriate.

Sonidegib has beneficial lipophilicity in comparison to vismodegib, making it preferable for tissue penetration.² The FDA approved sonidegib in 2015.

Mechanism of Action

Sonidegib is a biphenyl carboxamide that blocks the signaling in the hedgehog (Hh) pathway.³ It binds to and inhibits Smoothened, a transmembrane protein involved in Hh signal transduction.¹ This Hh signaling pathway is one of the pathways involved in cancer development.

Clinical Trials

The clinical trial BOLT evaluated the safety and efficacy of sonidegib. Researchers randomized patients (2:1) to receive either sonidegib 800 mg or 200 mg.

Of the 66 patients receiving 200 mg, 37 patients had either partial or complete responses after 30 months. The study defined a complete response as disappearance of all lesions.

In patients taking 800 mg, there was no evidence of better antitumor patients.⁴ Currently, the FDA only approves sonidegib to treat locally advanced BCC and metastatic BCC, however, researchers are investigating it for use in treatment of other cancer types.

These types include renal cell carcinoma, lung cancer, myeloid leukemia, pancreatic cancer, and lymphoma.

Dosage and Administration

Sonidegib comes in 200 mg capsules taken by mouth once daily. Patients should take sonidegib on an empty stomach, at least 1 hour before or 2 hours after a meal. Providers should obtain serum creatinine kinase (CK) levels and renal function tests prior to administration in all patients.

Adverse Events (AEs)

Patients taking sonidegib may experience abdominal pain, alopecia, diarrhea, decreased weight or appetite, fatigue, nausea, or pruritis. Musculoskeletal AEs occurred in 68% of patients treated with sonidegib 200 mg in the BOLT study.

These reactions include muscle spasms, musculoskeletal pain, and myalgia. If a patient experiences musculoskeletal symptoms, providers should consider a temporary dose interruption or discontinuation based on severity. Pharmacists should counsel patients to watch for all possible AEs and report to providers as soon as possible.

Warnings and Contraindications

Patients taking sonidegib must avoid strong CYP3A4 inhibitors. This is because CYP3A is the primary metabolizer of sonidegib. In trials, pediatric patients exposed to sonidegib reported premature fusion of the epiphyses which is why pediatric patients should not use this drug.

Pregnancy and Lactation

Pregnant patients must avoid taking sonidegib due to the severe birth defects it can cause. Sonidegib is embryotoxic, fetotoxic, and teratogenic.

Female patients of reproductive potential should use effective contraception during and at least 20 months after treatment with sonidegib. There is a risk of exposure to sonidegib through semen.

Males taking sonidegib should use condoms with a pregnant partner or a female partner or reproductive potential. Patients should not donate blood or blood products while taking sonidegib and for at least 20 months after their last dose because their blood products may be given to a female of reproductive potential.

There are no data regarding the presence of sonidegib in breast milk. However, due to the potential for serious AEs in breastfed infants, women should not breastfeed during treatment with sonidegib and for at least 20 months after the last dose.

About the Author

Greta Staubly is a 2024 PharmD candidate at the University of Connecticut.

References

1. Odomzo.com. 2019. Highlights of Prescribing Information. [online] Available at: <https://www.odomzo.com/themes/custom/odomzo/global/pdfs/pi.pdf> [Accessed 24 May 2022].
2. Dummer R, Ascierto PA, Basset-Seguin N, et al. Sonidegib and vismodegib in the treatment of patients with locally advanced basal cell carcinoma: a joint expert opinion. J Eur Acad Dermatol Venereol. 2020;34(9):1944-1956. doi:10.1111/jdv.16230
3. Jain S, Song R, Xie J. Sonidegib: mechanism of action, pharmacology, and clinical utility for advanced basal cell carcinomas. Onco Targets Ther. 2017; 10:1645-1653. Published 2017 Mar 16. doi:10.2147/OTT.S130910
4. National Center for Biotechnology Information. PubChem Compound Summary for CID 24775005, Sonidegib. https://pubchem.ncbi.nlm.nih.gov/compound/Sonidegib. Accessed May 24, 2022.