Sonidegib efficacy and tolerability in advanced basal cell carcinoma: A single-center real-life experience

Abstract

To the Editor: There are little real-life data regarding sonidegib efficacy and tolerability for the treatment of locally advanced basal cell carcinoma (BCC).1Villani A. Fabbrocini G. Costa C. Scalvenzi M. Sonidegib: safety and efficacy in treatment of advanced basal cell carcinoma.Dermatol Ther (Heidelb). 2020; 10: 401-412https://doi.org/10.1007/s13555-020-00378-8Google Scholar, 2Dummer R. Ascierto P.A. 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: 1944-1956https://doi.org/10.1111/jdv.16230Google Scholar, 3Villani A. Megna M. Fabbrocini G. et al.Long-term efficacy of vismodegib after its withdrawal and patients' health-related quality of life using the dermatology life quality index (DLQI).Dermatol Ther (Heidelb). 2019; 9: 719-724https://doi.org/10.1007/s13555-019-00323-4Google Scholar This single-center retrospective study included adult patients with locally advanced BCC and multiple BCCs treated with sonidegib (200 mg/daily) from February 1, 2020, to April 30, 2021. Age, sex, diameter, localization, and histological subtype of the largest (target) lesion were recorded. Patients were visited every month, and laboratory examinations included blood count and creatine phosphokinase level; adverse events (AEs) related to the drug were reported. The primary objective was to evaluate the therapeutic response to sonidegib, defined as complete response (CR), clinical absence of all BCCs; partial response, >30% clinical reduction of the target BCC; and no response, <30% clinical reduction of the target lesion. Secondary objectives were time to CR and recurrence-free survival. Fifty-four patients (38 men and 16 women) with 144 BCCs were treated with sonidegib at the approved dosage of 200 mg daily. The median age at diagnosis was 77.8 years (range, 53-99 years). A total of 36 patients presented with a single target lesion that was a locally advanced BCC (15 nodular; 13 infiltrative, morpheaform, or micronodular; 3 superficial; 3 mixed; and 2 basosquamous) with a median tumor diameter of 4.2 cm; 18 patients presented with multiple primary BCCs. With regard to the anatomical site of the locally advanced BCCs, 25 (69.4%) were localized on the head and neck region, 6 (16.7%) on the trunk, 3 (8.3%) on the legs, and 2 (6.6%) on the upper limbs. The median time of treatment was 7.2 months. Of 54 patients, 29 (53.7%) achieved CR, 21 (38.9%) achieved partial response, and 4 were assessed as nonresponders. No baseline characteristic was associated with treatment outcome. Patients reporting CR were treated for a median time of 7 months. Of 21 patients who achieved partial responses, 16 (76.1%) discontinued treatment due to multiple AEs after a median time of 10 months. In patients who achieved CR, the median duration of follow-up was 5.6 months; 26 of 29 patients (89.6%) remained free of recurrence, and 3 patients (10.4%) recurred. The therapeutic response in our real-life data was higher than the rates reported in previous clinical trials4Chen L. Silapunt S. Migden M.R. Sonidegib for the treatment of advanced basal cell carcinoma: a comprehensive review of sonidegib and the BOLT trial with 12-month update.Future Oncol. 2016; 12: 2095-2105https://doi.org/10.2217/fon-2016-0118Google Scholar; this result might be due to the lack of histological confirmation in all the treated lesions. In line with premarketing trials, 46 (85.1%) patients experienced at least 1 AE; muscle spasms, dysgeusia, weight loss, and alopecia were the AEs most frequently reported in 89.1% (n = 41), 82.6% (n = 39), 58.7% (n = 27), and 43.5% (n = 20) of patients, respectively. Most patients reported mild-moderate grades of AEs (grade 1 or 2) (US Department of Health and Human Services National Institutes of Health National Cancer Institute, 2009). In conclusion, our real-life data confirmed the long-term efficacy and tolerability of sonidegib; however, our study is limited by the retrospective design. New studies on a larger cohort of patients with longer-term follow-up are still required. None disclosed.