Outcomes of Vismodegib for Periocular Locally Advanced Basal Cell Carcinoma From an Open-label Trial

Abstract

IMPORTANCEThe outcomes of vismodegib treatment in a relatively large cohort of study participants with periocular locally advanced basal cell carcinoma (POLA-BCC) may guide physicians when considering this treatment.OBJECTIVE To report the outcomes of vismodegib treatment in patients with POLA-BCC in the Safety Events in Vismodegib (STEVIE) study. DESIGN, SETTING, AND PARTICIPANTSThis post hoc subgroup analysis from the STEVIE single-arm, multicenter, open-label cohort study screened all 1215 participants for ocular or periocular involvement and identified 244 participants with POLA-BCC or metastatic BCC. Data for the first STEVIE trial were collected from 167 treatment locations in 36 countries from June 30, 2011, to June 14, 2017. This post hoc analysis was performed from April 1 to August 31, 2019. MAIN OUTCOMES AND MEASURESResponse to treatment and adverse events. RESULTS Ocular or periocular involvement was found in 244 of 1215 STEVIE participants (20.1%), who constituted the analytic sample. The median age of the study participants was 72.0 (interquartile range [IQR], 60.0-82.0]) years, and they included 143 men (58.6%). Locally advanced BCC was diagnosed in 238 of the 244 participants (97.5%) and metastatic BCC, in 6 (2.5%). The median duration of exposure to vismodegib was 40.0 (IQR, 20.0-78.0) weeks, specifically 39.7 (IQR, 19.9-76.0) weeks for POLA-BCC and 92.4 (IQR, 53.2-163.0) weeks for metastatic BCC. Sixty-nine participants (28.3%) sustained serious adverse events (alopecia, muscle spasms, dysgeusia, weight loss, decreased appetite, asthenia, ageusia, nausea, fatigue, and diarrhea). Two hundred thirty-two study participants (95.1%) sustained more than 1 adverse effect. The overall mean (SD) number of drug-related adverse effects per study participant by first adverse event, regardless of the severity, was 5.48 (3.84). Discontinuation of vismodegib treatment owing to an adverse event was recorded in 58 participants (23.8%). During the study, 22 participants (9.0%) died, 70 (28.7%) achieved complete response, and 94 (38.5%) achieved partial response. CONCLUSIONS AND RELEVANCEVismodegib was well tolerated by the study participants with POLA-BCC. The safety of vismodegib treatment according to the STEVIE trial findings is consistent with that reported in previous studies. These data may be helpful when considering vismodegib for patients with POLA-BCC.

Vismodegib for Preservation of Visual Function in Patients with Advanced Periocular Basal Cell Carcinoma: The VISORB Trial

“…The pivotal study, a prospective nonrandomized clinical trial, revealed a 43% response rate among patients with locally advanced BCC and 30% response rate among patients with metastatic BCC, with a median duration of response of 7.6 months [ 8 ]. Prospective trials have assessed vismodegib as a neoadjuvant in a variety of body locations [ 17 , 18 , 19 ], and several case studies have highlighted the efficacy of vismodegib for preserving vision in patients with orbital BCC [ 20 , 21 , 22 , 23 , 24 , 25 ]. More recently, post hoc prospective analysis of the multisite multicountry Safety Events in Vismodegib study data showed either complete or partial response to vismodegib in 67% of patients [ 25 ].…”

“…Prospective trials have assessed vismodegib as a neoadjuvant in a variety of body locations [ 17 , 18 , 19 ], and several case studies have highlighted the efficacy of vismodegib for preserving vision in patients with orbital BCC [ 20 , 21 , 22 , 23 , 24 , 25 ]. More recently, post hoc prospective analysis of the multisite multicountry Safety Events in Vismodegib study data showed either complete or partial response to vismodegib in 67% of patients [ 25 ]. However, to date, no prospective trials have specifically assessed whether vismodegib treatment preserves visual function.…”

Alternative treatment options for periocular basal cell carcinoma: a narrative review

“…The patient's cohort consisted of 244 participants with periocular locally advanced basal cell carcinoma (POLA-BCC). The study showed that Vismodegib in periocular use showed a comparable side-effects profile than in non-ocular BCC (20). Another review conducted for the periocular treatment with Vismodegib reports a complete regression of 30% of patients, with follow-up less than 5 months.…”

New Targeted Therapies and Immunotherapies for Locally Advanced Periocular Malignant Tumours: Towards a New ‘Eye-Sparing’ Paradigm?

“…In addition, serious anti-SMO side effects should not be neglected. In their study involving 244 periocular BCCs, [ 19 ] found that 5.7% of patients died from anti–SMO-related side effects, whereas only 2% died from disease progression [ 19 ]. This finding should be kept in mind, especially in more fragile and elderly patients.…”