title: Clinical benefit assessment of vismodegib therapy in patients with advanced basal cell carcinoma.
abstract: OBJECTIVE
  Vismodegib was approved for the treatment of advanced basal cell carcinoma (aBCC) based on the pivotal ERIVANCE BCC study. The primary endpoint (objective response rate [ORR]) was assessed 9 months after the last patient was enrolled. To confirm the clinical benefit of vismodegib, an additional analysis was performed 12 months after the primary analysis.
  
  
  METHODS
  ERIVANCE BCC was a multicenter, nonrandomized, two-cohort study of 104 patients with histologically confirmed aBCC. Patients received 150 mg oral vismodegib daily until disease progression, intolerable toxicity, or withdrawal. An independent review panel comprising three expert clinicians reviewed patient photographs individually and as a consensus panel to evaluate baseline disease severity and clinical benefit after vismodegib treatment in 71 patients with locally advanced BCC (laBCC).
  
  
  RESULTS
  Sixty-three patients were efficacy evaluable; baseline and postprogression photographs for 61 were available for review. Baseline disease severity was judged as 5 or 4 (very severe or moderately severe) in 71.4%. Clinical benefit was observed in 76.2% (significant: 65.1%; some: 11.1%). Interpanelist agreement (maximum difference ≤1 point among panelists' scores in 65.1% and 87.3% of patients for clinical benefit and baseline disease severity, respectively) and correlation between individual and panel reviews were strong. Clinical benefit scores showed good concordance with the protocol-specified ORR obtained by an independent review facility and with investigator-assessed response.
  
  
  CONCLUSIONS
  Clinical benefit assessed by independent review based on expert clinical judgment provides strong evidence that treatment with vismodegib results in clinically meaningful and durable responses in patients with laBCC.
authors.affiliation: CHU de Nantes, Nantes, France; Hôpital Saint-Louis, Paris, France; Genentech, Inc., South San Francisco, California, USA; Universitätsklinikum Essen, Essen, Germany brigitte.dreno@wanadoo.fr.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Dreno
authors.affiliation: CHU de Nantes, Nantes, France; Hôpital Saint-Louis, Paris, France; Genentech, Inc., South San Francisco, California, USA; Universitätsklinikum Essen, Essen, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Basset-Seguin
authors.affiliation: CHU de Nantes, Nantes, France; Hôpital Saint-Louis, Paris, France; Genentech, Inc., South San Francisco, California, USA; Universitätsklinikum Essen, Essen, Germany.
authors.forename: Ivor
authors.initials: I
authors.lastname: Caro
authors.affiliation: CHU de Nantes, Nantes, France; Hôpital Saint-Louis, Paris, France; Genentech, Inc., South San Francisco, California, USA; Universitätsklinikum Essen, Essen, Germany.
authors.forename: Huibin
authors.initials: H
authors.lastname: Yue
authors.affiliation: CHU de Nantes, Nantes, France; Hôpital Saint-Louis, Paris, France; Genentech, Inc., South San Francisco, California, USA; Universitätsklinikum Essen, Essen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schadendorf
mesh_terms: D000328:Adult; D000368:Aged; D000813:Anilides / Q000008:administration & dosage* / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002280:Basal Cell Carcinoma / Q000188:drug therapy* / Q000473:pathology; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; C538724:HhAntag691; D011725:Pyridines
keywords: Advanced basal cell carcinoma; Clinical benefit; ERIVANCE BCC; Independent panel review; Vismodegib