Safety and efficacy of vismodegib in patients with basal cell carcinoma nevus syndrome: pooled analysis of two trials

Abstract

BackgroundAberrant activation of the Hedgehog (Hh) pathway is a key driver in the pathogenesis of basal cell carcinomas (BCCs), including patients with BCC nevus syndrome (BCCNS). It is unclear whether BCCs arising in patients with BCCNS respond differently to vismodegib than in patients without BCCNS. We examined the best overall response rate (BORR) and adverse events (AEs) of vismodegib in patients with advanced BCC (aBCC) with and without BCCNS.MethodsPatients were treated with vismodegib 150 mg/day in the ERIVANCE BCC trial (ClinicalTrials.gov number, NCT00833417) and the expanded access study (EAS; ClinicalTrials.gov number, NCT01160250). BCCNS diagnosis was based on medical history at the time of enrollment. Metastatic BCC response was evaluated using Response Evaluation Criteria In Solid Tumors, version 1.0 (RECIST v1.0) in both studies. Locally advanced BCC was evaluated by a novel composite end point in ERIVANCE BCC and by RECIST v1.0 in the EAS. Response assessments were performed every 8 weeks in ERIVANCE BCC and every 8–16 weeks in the EAS. Safety assessments (National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0) were performed monthly in both trials. Because of described differences in response assessment/schedule, patients with BCCNS were not pooled across trials. Analytic cohorts for BCCNS and sporadic aBCC were created within each trial for comparison using descriptive statistical methods.ResultsForty-one patients with BCCNS were included in the study: 22 from ERIVANCE BCC and 19 from the EAS. Investigator-assessed BORR in BCCNS groups ranged from 31 to 81 % in patients with locally advanced BCC (n = 33) and was 50 % in patients with metastatic BCC (n = 6). These results were comparable with the non-BCCNS groups. Incidence and severity of AEs were also comparable between the BCCNS and non-BCCNS groups. Amenorrhea was observed in both patient cohorts and was reversible in two patients who discontinued treatment.ConclusionVismodegib demonstrated comparable efficacy and safety against aBCC in patients with and without BCCNS.

Drug holiday approach for Vismodegib treatment in patients with nevoid basal cell carcinoma syndrome: Three cases from real clinical practice

“…Vismodegib has demonstrated clinical activity in patients with BCC with and without BCCNS with an overall similar safety profile in both groups. 2 However, in patients with BCCNS BCCs are a chronic condition that needs lifelong treatment. 3 Because of this, the psychological exhaustion caused by the chronicity of AEs that otherwise could be considered trivial appears as the main limiting factor in the persistence of the drug.…”

Vismodegib in the treatment of basal cell carcinoma — Polish clinical experience in the frame of therapeutic program

“…In 2016 Chang et al evaluated the effectiveness of treatment of patients with Gorlin-Goltz syndrome, qualified as laBCC or mBCC in the ERIVANCE and EAS studies [13]. In the ERIVANCE study all patients diagnosed with GGS were in the laBCC group (21/63), while in the EAS study 12/56 study in the laBCC group and 6/39 in the mBCC group.…”

Scalping Surgery – Dermatologic Indications beyond Curative Primary Skin Cancer Surgery

“…In a pooled analysis of two vismodegib trials by Chang et al (2016), 46 patients with Gorlin-Goltz syndrome were included. The investigator-rated best overall response reached 31 to 81 % in patients with unresectable BCC (n = 33) and 50 % in patients with metastatic BCC (n = 6) [ 20 ]. On the other hand, there is increasing evidence for either primary or secondary tumour resistance to hedgehog inhibitors, the transformation of BCC to squamous cell carcinoma (SCC) and increased risk of development of cutaneous SCC after vismodegib therapy [ 21 - 23 ].…”