Manufacturer:

Genentech, Inc.

Pharmacological Class:

Hedgehog pathway inhibitor.

Active Ingredient(s):

Vismodegib 150mg; caps.

Indication(s):

Treatment of adults with metastatic basal cell carcinoma, or locally advanced basal cell carcinoma that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation.

Pharmacology:

Vismodegib is an inhibitor of the Hedgehog pathway. Vismodegib binds to and inhibits Smoothened, a transmembrane protein involved in Hedgehog signal transduction.

Clinical Trials:

A single-arm, open-label, 2-cohort trial was conducted in 104 patients with either metastatic basal cell carcinoma (mBCC) (n=33) or locally advanced basal cell carcinoma (laBCC) (n=71). Patients with laBCC were required to have lesions that had recurred after radiotherapy, unless radiotherapy was contraindicated or inappropriate, and where the lesions were either unresectable or surgical resection would result in substantial deformity. Patients were to receive 150mg vismodegib per day until disease progression or unacceptable toxicity.

The major efficacy outcome measure was objective response rate (ORR) as assessed by an independent review faculty. In the mBCC cohort, tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. In the laBCC cohort, tumor response evaluation included measurement of externally assessable tumor (including scar) and assessment for ulceration in photographs, radiographic assessment of target lesions (if appropriate), and tumor biopsy. An ORR in laBCC required at least one of the following criteria and absence of any criterion for disease progression: ≥30% reduction in lesion size [sum of the longest diameter (SLD)] from baseline in target lesions by radiographic assessment; ≥30% reduction in SLD from baseline in externally visible dimension of target lesions; or complete resolution of ulceration in all target lesions. Complete response was defined as ORR (as defined previously) with no residual BCC on sampling tumor biopsy. Disease progression was defined as any of the following: ≥20% increase in the SLD from nadir in target lesions (either by radiography or by externally visible dimension); new ulceration of target lesions persisting without evidence of healing for at least 2 weeks; new lesions by radiographic assessment or physical examination; or progression of non-target lesions by RECIST.

The study demonstrated that Erivedge shrank lesions (objective response rate, or ORR) in 43% (27/63) of patients with locally advanced BCC and 30% of patients (10/33) with metastatic BCC, as assessed by independent review. The median duration of response was 7.6 months.

Legal Classification:

Rx

Adults:

Swallow whole. 150mg once daily, until disease progression or unacceptable toxicity.

Children:

Not established.

Warnings/Precautions:

Risk of embryo-fetal death and severe birth defects in pregnant women. Verify pregnancy status prior to initiation of therapy. Counsel patients (males and females) on the need for contraception during and after treatment. Advise patients not to donate blood or blood products while on therapy and for at least 7 months after last dose. Pregnancy (Cat.D). Nursing mothers: not recommended.

Interaction(s):

May be potentiated by P-gp inhibitors (eg, clarithromycin, erythromycin, azithromycin). May be antagonized by drugs that affect gastric pH (eg, proton pump inhibitors, H₂-receptor antagonists, antacids).

Adverse Reaction(s):

Muscle spasms, alopecia, dysgeusia, weight loss, fatigue, GI upset, decreased appetite, constipation, arthralgias, ageusia.

Notes:

Report immediately exposure to Erivedge during pregnancy by contacting the Genentech Adverse Event Line at (888) 835-2555.

How Supplied:

Caps—28