FDA Approval for Vismodegib
Brand name: Erivedge®
- To treat metastatic or recurrent locally advanced basal cell carcinoma in adults who cannot be treated with surgery or radiation
Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions, and contraindications.
On January 30, 2012, the Food and Drug Administration (FDA) approved vismodegib (Erivedge® Capsule, made by 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 the 96 patients with confirmed BCC. The patients had a median age of 62 years, 61 percent were male, and 97 percent had an ECOG performance status of 0 or 1. Twenty-one percent of patients were diagnosed with Gorlin syndrome. Sixty-six percent had locally advanced disease; 34 percent had metastatic disease. Among those with mBCC, 97 percent were previously treated. The prior therapies included surgery (97 percent of patients), radiotherapy (58 percent), and systemic therapies (30 percent). Among laBCC patients, 94 percent were previously treated. Prior therapies included surgery (89 percent), radiotherapy (27 percent), and systemic/topical therapies (11 percent).
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 patients with mBCC.
The ORRs were 30.3 percent (95 percent CI: 15.6, 48.2) in patients with mBCC and 42.9 percent (95 percent CI: 30.5, 56.0) in patients with laBCC. All responses in the mBCC cohort were partial responses. For the 63 evaluable patients with laBCC, 13 patients (20.6 percent) had complete responses and 14 patients (22.2 percent) had partial responses. The median response durations were 7.6 months (95 percent CI: 5.6, not estimable) for patients with MBCC and 7.6 months (95 percent CI: 5.6, 9.7) for patients with laBCC.
Safety was evaluated in 138 patients who received vismodegib as monotherapy for laBCC or mBCC. Adverse reactions occurring in more than 10 percent 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 premenopausal women developed amenorrhea. Grade 3 adverse reactions occurring in more than 1 percent 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.
This summary was provided by Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products.
The FDA is the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs and other products. (See "Learn How Drugs and Devices Get Approved.") The FDA's mission is to promote and protect the public health by helping safe and effective products to reach the market in a timely way, and monitoring products for continued safety after they are in use.