Clinical decision-making and adjustments involved in prescribing SMOi for advanced BCC is nuanced. Findings from our survey suggest a prescribing preference for vismodegib despite providers believing them to be comparable medication options, if not superior tolerability in sonidegib. Although vismodegib was prescribed more frequently, the data from ERIVANCE and BOLT, when compared with modified criteria, suggest a comparable, if not inferior, tolerability and AE profile compared to sonidegib [7].
As expected, AEs were the most difficult aspect of managing SMOi. Clinicians were more inclined to switch from vismodegib to sonidegib when AEs were problematic, which could indicate a perceived advantage in tolerability for sonidegib. The clinical decision to switch from vismodegib to sonidegib is supported by prior and original pivotal trial studies. Vismodegib had a notably high rate of 98% of patients experiencing AE in the STEVIE trial [2]. In comparison, analysis of sonidegib in BOLT revealed that only 43% of patients in the 200 mg group experienced AEs [5]. Studies have demonstrated successful reductions in AE when switching from vismodegib to sonidegib, although there is potential that the benefit arises from the drug holiday, rather than from the other SMOi [6]. Relatedly, our study highlighted clinicians’ strategies to implement various dosing regimens, including 1 month on, 1 month off; 2 weeks on, 2 weeks off; and every other day. Alternative dosing has been studied with success with vismodegib regarding improved tolerability and is also utilized in clinical practice for sonidegib [3,12].
Over two-thirds of respondents in this study believed that the two medications had the same incidence of AEs or did not know which medication had higher incidence (Table I). Given that AE are the most common reason for discontinuation and have major implications on treatment outcomes and patient quality of life, dermatologists’ familiarity with these drug profiles is crucial [8]. Emerging data have strongly reflected higher tolerability of sonidegib. The CARADERM real-world trial demonstrated significantly lower cumulative incidence of AE, severity of AE, and notably high discontinuation rates due to clinical benefit at 12 months, rather than AE (50% vs 30%) [1, 9].
Data from landmark trials are important, though they provide challenges for clinical interpretation. Clinician discrepancies in knowledge were evidenced in our findings regarding accurate knowledge of the pharmacokinetic profiles, median duration of response, and median progression-free survival between vismodegib and sonidegib. As immunotherapies are becoming relied upon for advanced BCC treatment in the refractory or intolerability setting, increasing provider education about the differences in SMOi medications will be critical to balancing therapeutics with tolerability, as well as potentially utilizing them earlier or in a wider range of clinical scenarios.
Results of prescribing preferences of these experts in multiple fields highlight the lack of familiarity and uniformity with the therapeutic options of SMOi for advanced BCC. Updating SMOi clinical guidelines and the creation of management strategies, including considerations for AE, dosing options, and drug switching, are needed to improve and standardize patient care. Although sample size was limited, insights from this study underscore the importance of personalized treatment strategies and considering patient-specific tolerability. Clinically, this data supports the need for a flexible approach to SMOi therapy and the importance of utilizing findings from real-world practice into clinical guidelines. Physician education will be critical in aligning physicians’ real-world use of SMOi with landmark and emerging clinical data.