Oral Hedgehog Inhibitor, Vismodegib, for Locally Advanced Periorbital and Orbital Basal Cell Carcinoma - IN PRESS

Abstract

A Report by the American Academy of Ophthalmology Ophthalmic Technology Assessment Committee Oculoplastics and Orbit Panel

Edward Wladis, MD,¹ Vinay K. Aakalu, MD, MPH,² M. Reza Vagefi, MD,³ Jeremiah P. Tao, MD, MD,⁴ Timothy J. McCulley, MD,⁵ Suzanne K. Freitag,⁶ Jill A. Foster, MD,^{7, 8} Stephen J. Kim, MD,⁹ 

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Purpose: To review the efficacy and safety of oral vismodegib (Erivedge; Genentech) in the management of locally advanced orbital and periorbital basal cell carcinoma (BCC).

Methods: A literature search was conducted last in September 2023 in the PubMed database for English language original research that evaluated the effect of oral vismodegib on orbital and periorbital BCC. Sixty articles were identified and 16 met the inclusion criteria.

Results: Most studies demonstrated high response rates, with up to 100% of patients responding to the medication in individual studies and initial complete regression occurring in up to 88% of patients. Vismodegib treatment resulted in significant reductions in tumor volume, resulting in globe preservation for most patients. However, in 12% of patients, the response was partial. Recurrences also occurred with substantial frequency, even after an initial complete response. As such, up to 79.4% of patients required surgical intervention, and up to 23% of patients still required exenteration. Use of these agents resulted in reductions in tumor volume that may delay or prevent the need for exenteration in some, but not all, patients. Importantly, molecular analysis of tissue excised after vismodegib therapy revealed persistent tumor in all patients, with frequent accumulation of mutations that may confer resistance to further hedgehog inhibitor therapy. Although most adverse events were rated as level I or II, side effects were common, with up to 100% of patients in studies experiencing at least 1 event. Muscle cramps, alopecia, weight loss, fatigue, and dysgeusia were the most common adverse events, and several patients discontinued therapy because of them. Furthermore, 1 patient died of sepsis that may have resulted from the therapy.

Conclusions: Although level I and II evidence are lacking, most studies indicate a benefit from the use of oral vismodegib to treat orbital and periorbital BCC tumor volume. However, patients should be cautioned about the adverse side effects of treatment and the persistence of tumor cells with mutations that may cause long-term resistance. Use of vismodegib as short-term neoadjuvant therapy may be effective in shrinking tumor volume to reduce surgical morbidity while reducing the frequency and severity of side effects.

¹Ophthalmic Plastic Surgery, Lions Eye Institute, Department of Ophthalmology, Albany Medical Center, Albany (Slingerlands), New York
²Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor Michigan
³Tufts University School of Medicine, Boston, Massachusetts
⁴Gavin Herbert Eye Institute, University of California, Irvine School of Medicine, Irvine, California
⁵Department of Ophthalmology, John P. McGovern Medical School, University of Texas Health Science Center, Houston, Texas
⁶Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts
⁷Ophthalmic Surgeons and Consultants of Ohio, Columbus, Ohio
⁸The Ohio State University, Ohio University Heritage College of Osteopathic Medicine, Athens, Ohio
⁹Department of Ophthalmology, Vanderbilt University School of Medicine, Nashville, Tennessee