Follow-Up of Patients With Complete Remission of Locally Advanced Basal Cell Carcinoma After Vismodegib Discontinuation: A Multicenter French Study of 116 Patients

Abstract

PURPOSE Vismodegib is a hedgehog pathway inhibitor indicated for the treatment of locally advanced basal cell carcinoma (laBCC), with an objective response rate of 65%, including a 32% complete response (CR). However, adverse effects often lead to drug discontinuation. The objective of our study was to evaluate long-term responses, predictive factors, and management of relapse after vismodegib discontinuation. METHODS An observational retrospective study was conducted in nine French oncodermatology units. We included patients with laBCC with CR on vismodegib who discontinued treatment between March 2012 and January 2016; we reviewed charts up to June 2016. The primary objective was to evaluate median relapse-free survival (RFS). Secondary objectives were risk factors associated with RFS, relapse, and death and treatment modalities after relapse and their efficacy. RESULTS One hundred sixteen patients with laBCC were included. The median RFS was 18.4 months (95% CI, 13.5 to 24.8 months). The RFS rate at 36 months was 35.4% (95% CI, 22.5% to 47.9%) for the total population and 40.0% (95% CI, 25.7% to 53.7%) for patients without Gorlin syndrome. LaBCC to the limbs and trunk was the only variable independently associated with a higher risk of relapse (hazard ratio, 2.77; 95% CI, 1.23 to 6.22; P = .019). Twenty-seven patients (50%) who experienced relapse during follow-up were retreated with vismodegib, with an objective response in 23 (objective response rate, 85%; CR rate, 37%; partial response rate, 48%) and eligibility for surgery in 24 (42%). CONCLUSION Long-term response after vismodegib discontinuation is frequent. Most patients who experience a relapse still respond to vismodegib rechallenge.

A Review of Hedgehog Inhibitors Sonidegib and Vismodegib for Treatment of Advanced Basal Cell Carcinoma

“…23 After 36 months of follow-up, the relapse-free rate was 35%. 23 The second study in 35 patients with advanced BCC who received 6 months of vismodegib treatment reported a 31% relapse rate after a 6-month follow-up. 24 There are no published studies evaluating relapse following discontinuation of sonidegib in patients who achieved CR.…”

“…22 Relapse following complete response Two retrospective studies examined relapse after discontinuation of vismodegib treatment in patients who achieved CR. 23,24 In the first study, 116 patients with laBCC, including those previously enrolled in STEVIE and MIKIE, reported a median (95% confidence interval [CI]) relapse-free survival of 18 (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24) months after CR and end of vismodegib treatment. 23 After 36 months of follow-up, the relapse-free rate was 35%.…”

Head and neck oncology during the COVID-19 pandemic: Reconsidering traditional treatment paradigms in light of new surgical and other multilevel risks

“…If or if not clearly curative, cemiplimab. [64] or vismodegib [65] may be considered. Neoadjuvant use of cemiplimab or vismodegib have not been adequately evaluated, [66] but may facilitate operative delays under extenuating circumstances.…”

Update in the Management of Basal Cell Carcinoma

“…In a recent report looking at long-term maintenance of CR after drug interruption, it was shown that 60% of patients have relapsed after 3 years of follow-up, with 40% (when BCCNS cases are excluded) having not relapsed at the time. Among relapsing patients, 48% had become eligible for surgery and 50% were vismodegib re-challenged and showed an ORR of 85% (42). Sonidegib.…”