From the Guidelines
Sonidegib is a viable treatment option for locally advanced basal cell carcinoma (BCC) that has recurred following surgery or radiation therapy, or for patients who are not candidates for surgery or radiation therapy, with a recommended dose of 200 mg/d. The efficacy of sonidegib for BCC is supported by the phase II BOLT trial, which compared two different doses of sonidegib in patients with locally advanced BCC or metastatic BCC 1. The trial demonstrated similar response rates for the two doses tested, with the higher dose (800 mg/d) associated with higher rates of serious adverse events (AEs) and AEs leading to dose interruptions, reductions, or discontinuation. Common AEs associated with sonidegib treatment include muscle spasms, dysgeusia, alopecia, nausea, weight decrease, and fatigue 1.
Key considerations for sonidegib treatment include the potential for advanced BCC to develop resistance, which limits the duration of response 1. Additionally, sonidegib has been shown to have limited efficacy in patients with vismodegib-resistant advanced BCC 1. Ongoing clinical research is exploring various dosing regimens of sonidegib in different BCC treatment settings, including less advanced disease or as part of primary treatment for previously untreated disease 1.
Regular monitoring of creatine kinase and liver function is recommended during sonidegib treatment, as elevated creatinine kinase is a common grade 3 to 4 AE 1. Furthermore, sonidegib is highly teratogenic, and effective contraception is mandatory during treatment and for at least 20 months after the last dose for both male and female patients of reproductive potential. Treatment typically continues until disease progression or unacceptable toxicity occurs, with most responses observed within the first 4-6 months of therapy.
In terms of quality of life, sonidegib treatment has been associated with a range of AEs that can impact patients' daily lives, including muscle spasms, hair loss, and taste disturbances 1. However, the efficacy of sonidegib in treating locally advanced BCC can also improve patients' quality of life by reducing tumor burden and alleviating symptoms associated with the disease. Overall, sonidegib is a valuable treatment option for patients with locally advanced BCC, and its use should be carefully considered in the context of individual patient needs and circumstances.
From the FDA Drug Label
ODOMZO (sonidegib) is indicated for the treatment of adult patients with locally advanced basal cell carcinoma (BCC) that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy. The efficacy of sonidegib for basal cell carcinoma (BCC) is established as it is indicated for the treatment of adult patients with locally advanced BCC that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy 2.
- Key points:
- Indicated for adult patients with locally advanced BCC
- Effective for BCC that has recurred following surgery or radiation therapy
- Also effective for patients who are not candidates for surgery or radiation therapy 2
From the Research
Efficacy of Sonidegib for Basal Cell Carcinoma (BCC)
- Sonidegib has been shown to be effective in the treatment of locally advanced basal cell carcinoma (laBCC) and metastatic BCC (mBCC) 3, 4, 5, 6.
- The multicentre BOLT trial demonstrated an objective tumour response rate of 36% (95% CI 24-50) and 34% (95% CI 25-43) in the sonidegib 200 mg and 800 mg once-daily groups, respectively 3.
- Central review of patients with laBCC showed that 43% achieved an objective response with sonidegib 200 mg once daily at the primary analysis date 3.
- The 42-month analysis of the BOLT study demonstrated sustained efficacy and a manageable safety profile, with objective response rates by central review of 56% (95% CI 43-68) for laBCC and 8% (95% CI 0·2-36) for mBCC in the 200-mg group 4.
Safety and Tolerability
- The majority of treatment-emergent adverse events were of mild to moderate severity and manageable with dosage adjustments, concomitant medications, and/or non-drug therapies 3.
- No new safety concerns emerged in the 42-month analysis of the BOLT study 4.
- Sonidegib and vismodegib, another hedgehog pathway inhibitor, have similar patterns of adverse events, but their pharmacokinetic profiles show several differences 7.
Comparison with Other Treatments
- Sonidegib and vismodegib have been compared in terms of their efficacy and safety profiles, with sonidegib demonstrating a slightly higher objective response rate (60.6% vs 47.6%) 7.
- The choice between sonidegib and vismodegib may depend on individual patient factors and clinical experience, as no head-to-head randomized controlled trials are available 7.