Key clinical-trial evidence for vismodegib

Author: Anoma Ranaweera,B.V.Sc; PhD (Clinical Biochemistry, University of Liverpool, UK),  Staff Writer, 2012.

The approval of vismodegib was based on results from the pivotal ERIVANCE Basal cell carcinoma (BCC) study.

ERIVANCE BCC was an international, single-arm, multicentre, two-cohort, open-label Phase II study that enrolled 104 patients with advanced BCC, including locally advanced BCC (n = 71) and metastasized BCC (33).

Locally advanced BCC patients had lesions that were inappropriate for surgery (inoperable, or for whom surgery would result in substantial deformity) and for which radiotherapy was unsuccessful or contraindicated.

Metastasized BCC was defined as BCC that had spread to other parts of the body, including the lymph nodes, lungs, bones and/or internal organs.

The 31 study sites were located in the United States, Australia and Europe. Study participants received 150mg vismodegib orally, once daily until disease progression or intolerable toxicity.

The trial showed that vismodegib substantially shrank tumours or healed visible lesions (objective response rate, or ORR) in 43 percent of patients with locally advanced BCC and 30 percent of patients with metastatic BCC, as assessed by independent review, the primary endpoint of the study.

The median progression-free survival (PFS) by independent review for both metastatic and locally advanced BCC patients was 9.5 months.

In addition, the clinical benefit rate (defined as patients who had a clinical response as well as those who experienced disease stability for more than 24 weeks) was 75 percent in patients treated with vismodegib.

In these patients, vismodegib shrank tumours or healed visible lesions, or prevented them from growing any further for more than 24 weeks.

The ORR as assessed by study investigators, a secondary endpoint, was 60 percent for locally advanced BCC and 46 percent for metastatic BCC.

Key results are tabulated below

ParameterMetastatic basal cell carcinoma
(n = 33 evaluable patients)
Locally-advanced basal cell carcinoma
(n = 63 evaluable patients)
Objective response rate, n (%) 10 (30.3)
[95% CI: 15.6, 48.2]
27 (42.9)
[95% CI: 30.5, 56.0]
Complete response, n (%) 0 13 (20.6)
Partial response, n (%) 10 (30.3) 14 (22.2)
Median response duration (months) 7.6
[95% CI: 5.6. not estimated]
[95% CI: 5.7, 9.7]

In the metastatic BCC cohort, tumour response was assessed according to the Response Evaluation Criteria in Solid tumours (RECIST) version 1.0.

RECIST is a set of published rules that define when cancer patients improve ("respond"), stay the same ("stabilise"), or worsen ("disease progression") during treatments.

The criteria were published in February, 2000 by an international collaboration including the European Organisation for Research and Treatment of Cancer (EORTC), National Cancer Institute of the United States, and the National Cancer Institute of Canada Clinical Trials Group.

In the locally advanced BCC cohort, tumour response evaluation included measurement of externally assessable tumour (including scar), assessment for ulceration in photographs, radiographic assessment of target lesions (if appropriate), and tumour biopsy.

Disease progression was defined as any of the following:

  • ≥ 20% increase in lesion size 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
  • progression of non-target lesions by RECIST.

An objective response in locally advanced BCC 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
  • complete resolution of ulceration in all target lesions.

Complete response in locally advanced BCC was defined as objective response (as defined above) with no residual BCC on sampling tumour biopsy.


Related Information


  • Lorusso PM, Jimeno A, Dy G, Adjei A, Berlin J, Leichman L, Low JA, Colburn D, Chang I, Cheeti S, Jin JY, Graham RA. Pharmacokinetic dose-scheduling study of hedgehog pathway inhibitor vismodegib (GDC-0449) in patients with locally advanced or metastatic solid tumors. Clin Cancer Res 2011 Sep 1; 17(17):5774-82.
  • Wong H, Alicke B, West KA, et al. Pharmacokinetic-pharmacodynamic analysis of vismodegib in preclinical models of mutational and ligand-dependent Hedgehog pathway activation. Clin Cancer Res 2011 Jul 15; 17(14):4682-92.
  • LoRusso PM, Rudin CM, Reddy JC, et al. Phase I trial of hedgehog pathway inhibitor vismodegib (GDC-0449) in patients with refractory, locally advanced or metastatic solid tumors. Clin Cancer Res 2011 Apr 15; 17(8):2502-11.
  • De Smaele E, Ferretti E, Gulino A. Vismodegib, a small-molecule inhibitor of the hedgehog pathway for the treatment of advanced cancers. Curr Opin Investig Drugs 2010 Jun; 11(6):707-18.
  • Dirix L, Migden MR, Oro AE et al. A pivotal multicenter trial evaluating efficacy and safety of the Hedgehog pathway inhibitor (HPI) vismodegib in patients with advanced basal cell carcinoma (BCC). Presented at the 2011 European Multidisciplinary Cancer Conference. Stockholm, Sweden. September 23-27, 2011. Abstract LBA1.
  • Patricia M. LoRusso, Sarina A. Piha-Paul, Alexander D. Colevas, Vikram Malhi et al. Pharmacokinetic assessment of drug-drug interaction potential when rosiglitazone or combined oral contraceptive is coadministered with vismodegib in patients with locally advanced or metastatic solid tumors. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10 (11 Suppl):Abstract no. B188.

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