title: U.S. Food and Drug Administration approval: vismodegib for recurrent, locally advanced, or metastatic basal cell carcinoma.
abstract: The data and regulatory considerations leading to the U.S. Food and Drug Administration (FDA) January 30, 2012 approval of Erivedge (vismodegib) capsules for the treatment of patients with recurrent, locally advanced, or metastatic basal cell carcinoma (BCC) are described. The FDA's approval decision was based primarily on the results observed in a single-arm, parallel cohort, international trial of vismodegib, administered orally at 150 mg daily until disease progression, in patients with pathologically confirmed, recurrent, locally advanced basal cell carcinoma (laBCC) or metastatic basal cell carcinoma (mBCC). An independent review committee confirmed an overall response rate (ORR) of 30.3% [95% confidence interval (CI): 15.6-48.2] in 33 patients with mBCC and an ORR of 42.9% (95% CI: 30.5-56.0) in 63 patients with laBCC; median response durations were 7.6 months and 7.6 months for patients with mBCC and laBCC, respectively. The most common adverse reactions were muscle spasms, alopecia, dysgeusia, weight loss, fatigue, nausea, diarrhea, decreased appetite, constipation, cough, arthralgias, vomiting, headache, ageusia, insomnia, and upper respiratory tract infection. Animal toxicology studies confirmed that vismodegib is a potent teratogenic agent. Approval was based on durable objective tumor responses supported by knowledge of the pathologic role of Hedgehog signaling in BCC and acceptable toxicity in a population without effective alternative therapies.
authors.affiliation: Office of Hematology and Oncology Products, Office of New Drugs, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland 20993, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Axelson
authors.forename: Ke
authors.initials: K
authors.lastname: Liu
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Jiang
authors.forename: Kun
authors.initials: K
authors.lastname: He
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.forename: Dubravka
authors.initials: D
authors.lastname: Kufrin
authors.forename: Todd
authors.initials: T
authors.lastname: Palmby
authors.forename: Zedong
authors.initials: Z
authors.lastname: Dong
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Russell
authors.forename: Sarah
authors.initials: S
authors.lastname: Miksinski
authors.forename: Patricia
authors.initials: P
authors.lastname: Keegan
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000813:Anilides / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002280:Basal Cell Carcinoma / Q000188:drug therapy* / Q000556:secondary; D017277:Drug Approval; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014481:United States; D014486:United States Food and Drug Administration; D055815:Young Adult
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; C538724:HhAntag691; D011725:Pyridines