A Study Evaluating the Efficacy and Safety of Vismodegib (GDC-0449, Hedgehog Pathway Inhibitor) in Patients With Advanced Basal Cell Carcinoma

OR=complete (CR) or partial response (PR). Metastatic-CR:Disappearance of all targets. PR:≥30% decreased sum of longest diameter (SLD) of targets compared to baseline (B). Locally advanced-Response=No progressive disease (PD) and ≥30% decreased SLD from baseline (radiography \[R\]) or ≥30% decreased SLD from B (externally visible dimension \[EVD\]) or completely resolved ulceration. CR:Response with no residual BCC on tumor biopsy (otherwise response was PR). PD:Any of ≥20% increased SLD from nadir (R or EVD), new ulceration, new lesions (R or physical exam) or non-target lesion progression by R.

Time frame: From study initiation (enrollment of first patient) through 9 months following the first treatment of the last enrolled patient (clinical cutoff date of 26 November 2010), up to 90 weeks

Population: Efficacy-evaluable population: All treated patients for whom the independent pathologist's interpretation of archival tissue or baseline biopsies was consistent with basal cell carcinoma.

The SF-36 Health Survey (Version 2) uses patient-reported symptoms on 8 subscales to assess health-related quality of life (HRQoL). The Physical Component Summary (PCS) score summarizes the subscales Physical Functioning, Role-Physical, Bodily Pain, and General Health. The Mental Component Summary (MCS) score summarizes the subscales Vitality, Social Functioning, Role-Emotional, and Mental Health. Each score was scaled from 0 to 100. A positive change score indicates better HRQoL.

Time frame: Baseline, Week 12, Week 24, and at the end of the study or early termination visit, up to 90 weeks

Population: Efficacy-evaluable population: All treated patients for whom the independent pathologist's interpretation of archival tissue or baseline biopsies was consistent with basal cell carcinoma.

Duration of OR was defined as the time from the initial CR or PR to the earliest documented disease progression (PD) or death. Metastatic BCC - PD: ≥ 20% increased sum of the longest diameter (SLD) of targets from nadir, or 1 or more new lesions. Locally advanced BCC - PD: any of: (1) ≥ 20% increased SLD from nadir (radiography or externally visible dimension); (2) new ulceration; (3) new lesions (radiography or physical exam); (4) progression of non-target lesions by radiography.

Time frame: From study initiation (enrollment of first patient) through 9 months following the first treatment of the last enrolled patient (clinical cutoff date of 26 November 2010), up to 90 weeks

Population: Efficacy-evaluable population: All treated patients for whom the independent pathologist's interpretation of archival tissue or baseline biopsies was consistent with basal cell carcinoma.

Overall survival was defined as the time from the initial dose of vismodegib until death from any cause.

Time frame: From study initiation (enrollment of first patient) through 9 months following the first treatment of the last enrolled patient (clinical cutoff date of 26 November 2010), up to 90 weeks

Population: Efficacy-evaluable population: All treated patients for whom the independent pathologist's interpretation of archival tissue or baseline biopsies was consistent with basal cell carcinoma.

In patients with locally advanced BCC, the histopathological effect of vismodegib was determined in tissue biopsies obtained at baseline and following vismodegib treatment. Reported are the percentage of patients with pathology confirmed BCC in baseline biopsy who had an absence of residual BCC post-baseline as assessed by an independent pathological review.

Time frame: From baseline through end of the study, up to 90 weeks

Population: Efficacy-evaluable population: All treated patients for whom the independent pathologist's interpretation of archival tissue or baseline biopsies was consistent with basal cell carcinoma. Only locally advanced BCC patients with available post-baseline biopsy assessed by an independent pathologist were included in the analysis.

PFS was defined as the time from start of treatment to the earliest documented disease progression (PD) or death. Metastatic BCC - PD: ≥ 20% increased sum of the longest diameter (SLD) of targets from nadir, or 1 or more new lesions. Locally advanced BCC - PD: any of: (1) ≥ 20% increased SLD from nadir (radiography or externally visible dimension); (2) new ulceration; (3) new lesions (radiography or physical exam); (4) progression of non-target lesions by radiography.

Time frame: From study initiation (enrollment of first patient) through 9 months following the first treatment of the last enrolled patient (clinical cutoff date of 26 November 2010), up to 90 weeks

Population: Efficacy-evaluable population: All treated patients for whom the independent pathologist's interpretation of archival tissue or baseline biopsies was consistent with basal cell carcinoma.