Background
Phase 2, multicenter, international, two-cohort, nonrandomized ERIVANCE BCC. N=96 advanced basal cell carcinoma (BCC): 33 metastatic (mBCC), 63 locally advanced (laBCC) not amenable to surgery or where surgery inappropriate. ~99% of advanced BCC harbor activating hedgehog pathway mutations. Vismodegib is the first-in-class oral Smoothened (SMO) inhibitor. Primary endpoint tested separately in each cohort.
Interventions and follow up
Treatment: Vismodegib 150 mg orally once daily continuously (single-arm)
Primary endpoint: Independently assessed ORR (CR+PR); hypothesis ORR >20% for laBCC and >10% for mBCC
mFollow up: NR
Primary endpoint: Independently assessed ORR (CR+PR); hypothesis ORR >20% for laBCC and >10% for mBCC
mFollow up: NR
Results
ORR (mBCC): 30.3% (10/33; 95% CI 16–48), P=.001
ORR (laBCC): 42.9% (27/63; 95% CI 31–56), P<.001; 13 CR (20.6%)
Median DOR: 7.6 months in both cohorts
ORR (laBCC): 42.9% (27/63; 95% CI 31–56), P<.001; 13 CR (20.6%)
Median DOR: 7.6 months in both cohorts
Adverse events
Most common (>30%): muscle spasms 71%, alopecia 65%, dysgeusia 55%, weight loss 45%, fatigue 40%
Serious AEs: 25%; 7 deaths attributed to adverse events
Grade 3–4: hyponatremia, dehydration, fatigue
Management: drug holidays required for tolerability in many patients
Serious AEs: 25%; 7 deaths attributed to adverse events
Grade 3–4: hyponatremia, dehydration, fatigue
Management: drug holidays required for tolerability in many patients
Conclusions
Vismodegib produced clinically meaningful ORRs in metastatic BCC (30%) and locally advanced BCC (43%), with 21% CR in laBCC — the first targeted therapy for advanced BCC. Established hedgehog pathway inhibition as the first systemic treatment and led to FDA approval.
Key Limitations
Single-arm, nonrandomized; no comparator. Small N (96); ORR surrogate endpoint. Substantial chronic toxicity drives discontinuation; median follow-up not reported.
Clinical Context
Vismodegib FDA-approved (2012) for metastatic and locally advanced BCC; first-line targeted option per ESMO for advanced disease unsuitable for surgery/radiation. Sonidegib is a second hedgehog inhibitor; cemiplimab follows after HHI failure.