Predictive Factors of Non-Response to Vismodegib in Locally Advanced Basal-Cell Carcinoma

Abstract

<b><i>Background:</i></b> Vismodegib has shown clinical efficacy in the management of locally advanced basal cell carcinomas (laBCC). However, non-response to vismodegib is observed in 2–13.5% of patients in clinical studies. The purpose of this study was to identify factors associated with non-response to vismodegib in patients with laBCC. <b><i>Methods:</i></b> We carried out a retrospective multicenter study, including patients with laBCC treated with vismodegib, from July 2011 to May 2019. Response to treatment was assessed according to the RECIST 1.1 criteria. Patients were categorized as responders with a complete response or a partial response or non-responders with a stable disease or a progressive disease according to what has been observed during follow-up. Patient demographics, tumor profile, and treatment modalities were compared in responders and non-responders. <b><i>Results:</i></b> Eighty-three patients with laBCC were included in the study. Twenty-five (30.1%) were non-responders to vismodegib. History of treatment with radiotherapy, presence of muscle involvement and intermittent treatment with vismodegib were significantly associated with a non-response (<i>p</i> < 0.001, <i>p</i> = 0.025, <i>p</i> < 0.001). Bone involvement (<i>p</i> = 0.2) and morpheaform IaBCC subtype (<i>p</i> = 0.056) were more frequent in non-responders without reaching statistical significance. <b><i>Conclusion:</i></b> In this study, non-response of laBCC to vismodegib therapy was associated with muscle involvement. Previous radiotherapy and intermittent use of vismodegib have been identified as causes favoring non-response to vismodegib. Due to the low numbers of patients included in the study, it is difficult to draw firm conclusions. Further studies are needed to confirm these data.

Clinical determinants of complete response to vismodegib in locally advanced basal cell carcinoma: a multicentre experience

“…Intermittent dosing was indeed recently reported as a cause favouring non-response to vismodegib. 9 In line with previous reports, we observed a median time to best response of 5.0 months and to CR of 4.9 months. 3,10 In our series, patients with toxicities more frequently achieved NCR to vismodegib.…”

Clinical Characteristics of an Italian Patient Population with Advanced BCC and Real-Life Evaluation of Hedgehog Pathway Inhibitor Safety and Effectiveness

“…Patients experiencing multiple AEs might undergo dose reduction or treatment discontinuation, which may affect tumor response outcomes. To this regard, some authors reported an association between intermittent dosing and nonresponse to HHI [18,20], while others claimed an unchanged efficacy profile [21][22][23].…”

Characterization of patients with advanced basal cell carcinoma progressing while receiving Hedgehog pathway inhibitors

“…Even though a recent study by Juzot et al (in preparation) did not report any predictive factors of response to vismodegib, similar data regarding radiotherapy have been reported in a small series of patients. 8 Nevertheless, as our data are retrospective, we must analyse these results with caution and a causal relationship cannot be asserted. The low number of events did not allow us to consider potential confounders (i.e.…”