Original article
Pivotal ERIVANCE basal cell carcinoma (BCC) study: 12-month update of efficacy and safety of vismodegib in advanced BCC

https://doi.org/10.1016/j.jaad.2015.03.021Get rights and content

Background

Primary analysis from the pivotal ERIVANCE BCC study resulted in approval of vismodegib, a Hedgehog pathway inhibitor indicated for treatment of adults with metastatic or locally advanced basal cell carcinoma (BCC) that has recurred after surgery or for patients who are not candidates for surgery or radiation.

Objective

An efficacy and safety analysis was conducted 12 months after primary analysis.

Methods

This was a multinational, multicenter, nonrandomized, 2-cohort study in patients with measurable and histologically confirmed locally advanced or metastatic BCC taking oral vismodegib (150 mg/d). Primary outcome measure was objective response rate (complete and partial responses) assessed by independent review facility.

Results

After 12 months of additional follow-up, median duration of exposure to vismodegib was 12.9 months. Objective response rate increased from 30.3% to 33.3% in patients with metastatic disease, and from 42.9% to 47.6% in patients with the locally advanced form. Median duration of response in patients with locally advanced BCC increased from 7.6 to 9.5 months. No new safety signals emerged with extended treatment duration.

Limitations

Limitations include low prevalence of advanced BCC and challenges of designing a study with heterogenous manifestations.

Conclusion

The 12-month update of the study confirms the efficacy and safety of vismodegib in management of advanced BCC.

Section snippets

Study design

The ERIVANCE BCC methods have been reported previously.7 Briefly, ERIVANCE BCC is a pivotal, phase-II, single-arm, 2-cohort, multicenter clinical trial to evaluate the efficacy and safety of vismodegib in patients with advanced BCC (ClinicalTrials.gov number NCT00833417). The study was conducted in accordance with FDA regulations and the International Conference on Harmonization E6 Guideline for Good Clinical Practice. The protocol was approved by an independent review board or ethics committee

Patient demographics and baseline characteristics

A total of 104 patients (mBCC n = 33, laBCC n = 71) were enrolled at 31 sites in the United States, Europe, and Australia. Eight patients in the laBCC cohort were excluded from efficacy analysis because they did not have histologically confirmed BCC by tumor biopsy performed at enrollment; however, all patients were considered safety evaluable (see Consolidated Standards of Reporting Trials [CONSORT] diagram [eFig 1]). Patient baseline characteristics have been previously described.7

Treatment exposure

At the data

Discussion

Vismodegib, an oral, selective inhibitor of the Hedgehog signaling pathway, which is critical in BCC pathogenesis,1, 5, 6 has been approved by the FDA as a treatment option for adult patients with a BCC.8, 9 Approval was based on results from the primary analysis of the pivotal ERIVANCE BCC study.7 The results presented here, after an additional 12 months of patient follow-up, confirm the results of the primary analysis and demonstrate durable responses to vismodegib treatment. At the

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This study was funded by F. Hoffmann-LaRoche and was designed by the investigators and representatives of the sponsor. The sponsor also was responsible for data collection and analysis. Medical writing assistance was provided by Saema Magre, PhD, Tony Serino, PhD, and David Gibson, PhD, CMPP, of ApotheCom (Yardley, PA) and was funded by F. Hoffmann-La Roche.

Dr Sekulic serves as a consultant for F. Hoffman-LaRoche (uncompensated). Dr Migden serves as a consultant for Genentech, Novartis, and Lilly and has received honoraria from Genentech, Novartis, and Lilly. Dr Lewis serves as a consultant for F. Hoffman-LaRoche, has received honoraria from F. Hoffman-LaRoche, and his institution has received grant funding for clinical trials from F. Hoffman-LaRoche. Dr Hainsworth's institution has received grant funding for clinical trials from Genentech. Dr Solomon is a consultant for Genentech, has received honoraria from Genentech, and his institution has received grant funding for clinical trials from Genentech. Dr Yoo is a consultant for Genentech, has received honoraria from Genentech, and his institution has received grant funding for clinical trials from Genentech. Dr Arron serves as a consultant for Genentech, Kythera, Allergan, Anacor, Lilly, and F. Hoffmann-LaRoche, has received salary from Genentech, Kythera, Allergan, Anacor, and Lilly, and has received honoraria from F. Hoffmann-LaRoche. Dr Friedlander serves as a consultant for Genentech and Bristol-Myers, has received honoraria from Genentech and Bristol-Myers Squibb, and his institution has received grant funding from Genentech. Dr Marmur serves as a consultant for Allergan and Dusa Pharmaceuticals. Dr Rudin serves as a consultant for Novartis and Lilly and has received honoraria from Novartis and Lilly. Dr Chang has received grants for clinical trials from F. Hoffmann-La Roche, Novartis, and Lilly. Dr Dirix declared no conflicts of interest. Dr Hou is an employee of Genentech and has received salary, stock options, and stock from Genentech. Dr Yue is an employee of F. Hoffmann-La Roche and has received salary, stock options, and stock from F. Hoffmann-LaRoche. Dr Hauschild serves as a consultant to Amgen, Bristol-Myers Squibb, Celgene, Eisai, GlaxoSmithKline, MedImmune, MelaSciences, Merck Serono, Merck, Novartis, Oncosec, and F. Hoffmann-LaRoche, received honoraria from Amgen, Bristol-Myers Squibb, Celgene, Eisai, GlaxoSmithKline, MedImmune, MelaSciences, Merck Serono, Merck, Novartis, Oncosec, and F. Hoffmann-LaRoche, and grants for clinical trials from Amgen, Bristol-Myers Squibb, Celgene, Eisai, GlaxoSmithKline, MelaSciences, Merck Serono, Merck, Novartis, Oncosec, and F. Hoffmann-LaRoche.

Supplementary data, eTables, and eFigures are available at http://www.jaad.org.

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