Efficacy and Safety of Vismodegib in Advanced Basal-Cell Carcinoma
By A. Sekulic, M. Migden, A. Oro, L. Dirix, K. Lewis, John Hainsworth, J. Solomon, S. Yoo, S. Arron, P. Friedlander and 9 more. New England Journal of Medicine, 2012
1,358 citations recorded by the source corpus.
BACKGROUND Alterations in hedgehog signaling are implicated in the pathogenesis of basal-cell carcinoma. Although most basal-cell carcinomas are treated surgically, no effective therapy exists for locally advanced or metastatic basal-cell carcinoma. A phase 1 study of vismodegib (GDC-0449), a first-in-class, small-molecule inhibitor of the hedgehog pathway, showed a 58% response rate among patients with advanced basal-cell carcinoma. METHODS In this multicenter, international, two-cohort, nonrandomized study, we enrolled patients with metastatic basal-cell carcinoma and those with locally advanced basal-cell carcinoma who had inoperable disease or for whom surgery was inappropriate (because of multiple recurrences and a low likelihood of surgical cure, or substantial anticipated disfigurement). All patients received 150 mg of oral vismodegib daily. The primary end point was the independently assessed objective response rate; the primary hypotheses were that the response rate would be greater than 20% for patients with locally advanced basal-cell carcinoma and greater than 10% for those with metastatic basal-cell carcinoma. RESULTS In 33 patients with metastatic basal-cell carcinoma, the independently assessed response rate was 30% (95% confidence interval [CI], 16 to 48; P = 0.001). In 63 patients with locally advanced basal-cell carcinoma, the independently assessed response rate was 43% (95% CI, 31 to 56; P<0.001), with complete responses in 13 patients (21%). The median duration of response was 7.6 months in both cohorts. Adverse events occurring in more than 30% of patients were muscle spasms, alopecia, dysgeusia (taste disturbance), weight loss, and fatigue. Serious adverse events were reported in 25% of patients; seven deaths due to adverse events were noted. CONCLUSIONS Vismodegib is associated with tumor responses in patients with locally advanced or metastatic basal-cell carcinoma. (Funded by Genentech; Erivance BCC ClinicalTrials.gov number, NCT00833417.)
Subfields: Dermatology, Epidemiology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/7013b9f6f1aa06ec65850a619ed6118262b52953
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Molecular Biology
Citations in the corpus
- Targeting cancer stem cell pathways for cancer therapy (2020, background): “599 Subsequently, phase I and phase II trials targeting recurrent medulloblastoma have shown that the progression-free survival (PFS) of Shh-mb patients treated with vismodegib is longer and more effective than that of non-Shh-mb patients.”
- Cancer Stem Cells (CSCs) in Drug Resistance and their Therapeutic Implications in Cancer Treatment (2018, background): “Vismodegib, a drug targeting HH pathway, was approved by the European Medicines Agency (EMA) in 2013 and the US FDA in 2012 for the therapy of metastatic BCC patients or locally advanced BCC patients that are not candidates for surgery or radiotherapy [176, 177].”