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U.S. Department of Health and Human Services

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Vismodegib

On January 30, 2012, the U. S. Food and Drug Administration approved vismodegib (ERIVEDGE Capsule, Genentech, Inc.) for the treatment of adults with metastatic basal cell carcinoma or with locally advanced basal cell carcinoma that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation.

Efficacy was demonstrated in a single-arm, parallel cohort trial enrolling 104 patients. Patients received 150 mg of vismodegib daily. Central pathologic review of archival or baseline tissue confirmed the diagnosis of basal cell carcinoma (BCC) in 96 patients: 33 patients with metastatic basal cell carcinoma (mBCC) and 63 patients with locally advanced basal cell carcinoma (laBCC).

Efficacy was evaluated in these 96 patients with confirmed BCC. The median age of this population was 62 years, 61% were male, and 97% had an ECOG performance status of 0 or 1. Twenty‑one percent of patients carried a diagnosis of Gorlin syndrome. Sixty-six percent had locally advanced disease; 34% had metastatic disease. Among those with mBCC, 97% were previously treated. Prior therapy included surgery (97%), radiotherapy (58%), and systemic therapies (30%). Among laBCC patients, 94% were previously treated. Prior therapies included surgery (89%), radiotherapy (27%), and systemic/topical therapies (11%).

The trial’s primary endpoint was objective response rate (ORR) assessed by an independent review facility. Tumor response criteria for laBCC included assessment of tumor size, the presence or absence of ulceration, and biopsy of local disease sites. The criteria for complete response in localized disease required tumor biopsy (ies) demonstrating no pathologic evidence of BCC. RECIST version 1.0 criteria were used to assess responses in the mBCC population.

The ORRs were 30.3% (95% CI: 15.6, 48.2) and 42.9% (95% CI: 30.5, 56.0) in patients with mBCC and laBCC, respectively. All responses in the mBCC cohort were partial responses. For the 63 evaluable patients with laBCC, 13 (20.6%) patients had complete responses and 14 (22.2%) had partial responses. The median response duration was 7.6 months (95% CI: 5.6, not estimable) and 7.6 months (95% CI: 5.6, 9.7) for patients with mBCC and laBCC, respectively.

Safety was evaluated in 138 patients who received vismodegib as monotherapy for laBCC or mBCC. Adverse reactions occurring in more than 10% of patients were muscle spasms, alopecia, dysgeusia, weight loss, fatigue, nausea, diarrhea, decreased appetite, constipation, arthralgias, vomiting, and ageusia. In clinical trials, a total of 3 of 10 pre-menopausal women developed amenorrhea. Grade 3 adverse reactions occurring in more than 1% of patients were weight loss, fatigue, muscle spasms, and decreased appetite.

Healthcare professionals should verify pregnancy status prior to the initiation of vismodegib, counsel pregnant women on the potential risks to the embryo/fetus, and advise non-pregnant women to use highly effective contraception during treatment with vismodegib and for up to 7 months after the last dose. To avoid exposing an embryo/fetus to vismodegib that may be contained in semen, male patients should use condoms with spermicide during treatment with vismodegib, and for 2 months after the last dose. Healthcare providers should report to Genentech any cases of exposure during pregnancy (either direct exposure in female patients or through seminal fluid from male patients), and should encourage pregnant women to participate in the Erivedge pregnancy pharmacogvigilance program to collect information on pregnancy outcomes.

Vismodegib inhibits the Hedgehog pathway, an important embryonic developmental pathway. Reproductive toxicology studies in rats demonstrated that vismodegib exposure during organogensis results in embryo-fetal death at higher exposures and severe birth defects at exposures within the range achieved with the recommended human dose. 

The recommended dose and schedule for vismodegib is 150 mg orally daily. Vismodegib may be taken with or without food.

Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203388lbl.pdf

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).