ERIVANCE: The Phase II pivotal trial that demonstrated clinically meaningful benefit in advanced BCC

INDICATION

Erivedge® (vismodegib) capsule is indicated 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.

Erivedge reduced disease burden as assessed visibly and histologically

ERIVANCE trial: Visible lesion reduction was achieved in 43% of locally advanced BCC patients4

Locally advanced BCC ORR by Independent Review 4,13

ORR=objective response rate.

Patients received at least 1 dose of Erivedge with independent pathologist-confirmed diagnosis of BCC. Locally advanced BCC patients were considered responders if they did not experience progression and had ≥30% reduction in lesion size (sum of the longest diameter) from baseline in target lesions by radiography or in externally visible dimensions of target lesions (scar tissue was measured); or had complete resolution of ulceration in all target lesions. Complete response was objective response with no residual BCC on sampling biopsy. Partial response was objective response with presence of residual BCC on sampling biopsy.

  • Median duration of response was 7.6 months (range, 1.0 to 12.9 months; 95% CI, 5.7–9.7)4,13
    • 13 of 27 responding patients were no longer considered responders due to an event (disease progression or death)13
  • Scar tissue was measured as part of the lesion when assessing response, as specified in the study protocol13
  • Independent Review evaluation of response included measurement of externally assessable lesion and assessment for ulceration in photographs, radiographic assessment of target lesions (if appropriate), and biopsy4

Erivedge reduced disease burden as assessed radiographically2,4,13

Erivedge was the first FDA-approved therapy for metastatic BCC

Metastatic BCC ORR by Independent Review 4,13

ORR=objective response rate.

Patients received at least 1 dose of Erivedge with independent pathologist-confirmed diagnosis of BCC. In the metastatic BCC cohort, response was assessed according to RECIST version 1.0. Complete response was disappearance of all target and nontarget lesions. Partial response was ≥30% decrease in sum of the longest diameter of target lesions from baseline.

  • Median duration of response was 7.6 months (range, 2.1 to 11.1 months; 95% CI, 5.6–not estimable) 4,13
    • 3 of 10 responding patients were no longer considered responders due to an event (disease progression or death) 2

Patients in the ERIVANCE trial received 150 mg Erivedge once daily until disease progression or intolerable toxicity 4,13

Patients continued Erivedge treatment until the following occurred:

Disease progression was defined as any of the following:

  1. ≥20% increase in the size of target lesions (as determined by radiography or externally visible dimensions)
  2. New ulceration of target lesions persisting without evidence of healing for at least 2 weeks
  3. New lesions as determined by radiographic assessment or physical examination
  4. Progression of nontarget lesions according to RECIST

Adverse reactions that led to discontinuation included*:

  • Muscle spasms (n=2)
  • Acute myocardial infarction (n=1)
  • Aphagia (loss of ability to swallow) (n=1)
  • Asthenia (lack or loss of strength) (n=1)
  • Death (n=1)
  • Fatigue (n=1)
  • Cellulitis (inflammation of connective tissue) (n=1)
  • Decreased weight (n=1)
  • Metastatic malignant melanoma (n=1)
  • Metastatic squamous cell carcinoma (n=1)
  • Dysgeusia (change in taste) (n=1)
  • Ischemic stroke (n=1)
  • Paresthesia (tingling sensation) (n=1)
  • Hypovolemic shock (n=1)

 

* Individual patients might have experienced ≥1 adverse reaction. The reason 15 adverse events are listed here is because 1 patient experienced muscle spasms, dysgeusia, and weight decrease.

Discontinuation due to patient choice 19.2% n=20

Underlying reason(s) for decision was not recorded


Patients remaining on treatment 49% n=51

All data as of November 2010 analysis.

BOXED WARNING

Embryo-Fetal Toxicity

  • Erivedge can cause embryo-fetal death or severe birth defects when administered to a pregnant woman. Erivedge is embryotoxic, fetotoxic, and teratogenic in animals. Teratogenic effects included severe midline defects, missing digits, and other irreversible malformations
  • Verify pregnancy status of females of reproductive potential within 7 days prior to initiating Erivedge therapy. Advise females of reproductive potential to use effective contraception during and after Erivedge therapy. Advise males of the potential risk of Erivedge exposure through semen and to use condoms with a pregnant partner or a female partner of reproductive potential. Advise pregnant women of the potential risks to a fetus

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INDICATION

Erivedge® (vismodegib) capsule is indicated 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.

BOXED WARNING AND ADDITIONAL IMPORTANT SAFETY INFORMATION

Embryo-Fetal Toxicity

  • Erivedge can cause embryo-fetal death or severe birth defects when administered to a pregnant woman. Erivedge is embryotoxic, fetotoxic, and teratogenic in animals. Teratogenic effects included severe midline defects, missing digits, and other irreversible malformations
  • Verify pregnancy status of females of reproductive potential within 7 days prior to initiating Erivedge therapy. Advise females of reproductive potential to use effective contraception during and after Erivedge therapy. Advise males of the potential risk of Erivedge exposure through semen and to use condoms with a pregnant partner or a female partner of reproductive potential. Advise pregnant women of the potential risks to a fetus
  • Advise female patients and female partners of male patients to contact their healthcare provider with a known or suspected pregnancy. Report pregnancies to Genentech at (888) 835‑2555

Female Patients

  • Advise females of reproductive potential to use effective contraception during therapy with Erivedge and for 24 months after the final dose

Male Patients

  • Advise males of the potential risk to an embryo or fetus if a female partner of reproductive potential is exposed to Erivedge. Advise male patients to use condoms with a pregnant partner or a female partner of reproductive potential, even after a vasectomy, during therapy and for 3 months after the final dose of Erivedge

Blood Donation

  • Advise patients not to donate blood or blood products while receiving Erivedge and for 24 months after the final dose of Erivedge

Semen Donation

  • Vismodegib is present in semen. It is not known if the amount of vismodegib in semen can cause embryo-fetal harm. Advise male patients not to donate semen during and for 3 months after the final dose of Erivedge

Premature Fusion of the Epiphyses

  • Premature fusion of the epiphyses has been reported in pediatric patients exposed to Erivedge. In some cases, fusion progressed after drug discontinuation

Adverse Reactions

  • The most common adverse reactions (≥10%) were muscle spasms, alopecia, dysgeusia, weight loss, fatigue, nausea, diarrhea, decreased appetite, constipation, arthralgias, vomiting, and ageusia
  • Amenorrhea can occur in females of reproductive potential. Reversibility of amenorrhea is unknown. In clinical trials, a total of 3 of 10 pre-menopausal women developed amenorrhea while receiving Erivedge
  • Treatment-emergent Grade 3 laboratory abnormalities observed in clinical trials were hyponatremia in 6 patients (4%), hypokalemia in 2 patients (1%), and azotemia in 3 patients (2%)
  • Additionally, in a post-approval clinical trial conducted in 1232 patients with locally advanced or metastatic BCC treated with Erivedge, a subset of 29 patients had baseline values for CPK reported. Within the subset of patients, 38% had a shift from baseline, and one of the patients had a Grade 3 value. The prevalence of Grade 3/4 CPK elevation across the entire study population with any CPK measurement was 2.4% (11 out of 453 patients)

Use in Specific Populations

Lactation

  • No data are available regarding the presence of vismodegib in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. Because of the potential for serious adverse reactions in breastfed infants from Erivedge, advise a nursing woman that breastfeeding is not recommended during therapy with Erivedge and for 24 months after the final dose

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.

Please see full Prescribing Information, including the BOXED WARNING and the Medication Guide, for a complete discussion of the risks associated with Erivedge.