• Vismodegib for Basal Cell Carcinoma


    During Saturday’s Oculofacial Plastic Surgery Subspecialty Day, Alon Kahana, MD, PhD, discussed the usefulness of vismodegib and sonidegib for basal cell carcinoma.

    Surgical treatment for recurrent and advanced basal cell carcinoma around the eye involves a unique problem, he said. Unlike cases of basal cell carcinoma on other parts of the body, “if you have it on the face, people care about the aesthetics, and if you have it around the eye, you may end up losing visual function.”

    Hedgehog inhibitors. Vismodegib (Erivedge) and sonidegib (Odomzo) are FDA-approved hedgehog pathway inhibitors. They are indicated for locally recurrent advanced basal cell carcinoma after surgery or for patients who are not candidates for surgery or radiation. Vismodegib is also indicated for metastatic cases.

    VISORB trial. The Vismodegib for Orbital and Periocular Basal Cell Carcinoma (VISORB) trial is a prospective trial conducted by Dr. Kahana, his colleague Shelby P. Unsworth, PhD, and their collaborators.

    “Everything I tell you about vismodegib should also apply to sonidegib,” Dr. Kahana added. “At the time of the initiation of this clinical trial, sonidegib had not yet been approved by the FDA.”

    Thus far, the trial has enrolled 35 patients; 31 have completed vismodegib treatment. By nine months, Dr. Kahana observed a high rate of clinical response. He noted that after treatment, more than 80% of patients had a stable or improved Visual Assessment Weighted Score (VAWS)—a metric the investigators developed for this study—indicating a positive visual function response.

    In addition, the team performed histologic analysis. Nine months after vismodegib treatment, pathology experts assessed H&E-stained tissue samples and reported no sign of disease in 63% of the cohort, while approximately 31% had disease present but were clear in the margins; only 5% had disease extending to the margin.

    Persistent versus resistant. Dr. Kahana noted that one patient experienced complete remission clinically at nine months but had recurrence at two years; this patient has now been followed for four years. Although this patient appeared histologically clear, keratin staining revealed keratin-positive microlesions near the peripheral margin; none were noted in the deep margin, however. The recurrent tumors were also much more positive for Gli1, an indicator of active hedgehog pathway signaling.

    “It’s one thing to have persistent tumor that is still amenable to vismodegib treatment or maybe it’s just inactive cells. It’s resistant, which means it can come back with a vengeance,” said Dr. Kahana. The clinical response, he explained, does not indicate complete histologic response.

    “This is not published. It has not yet gone for peer review, so take that with a grain of salt,” he noted, “but I’d like to share this with you so that in your treatment using this FDA-approved drug, you understand that there are some risks associated with it, and you need to be very careful.”

    Neoadjuvant potential? He proposed that around the eye, vismodegib and sonidegib may be best used as neoadjuvant therapies. Since recurrent tumors appearing after vismodegib treatment may be resistant to the drug, patients may ultimately need surgery. However, the hedgehog inhibitor may reduce the amount, complexity, and consequences of the surgery.

    “I think this [vismodegib] is an extraordinarily useful drug. It is not FDA indicated as a neoadjuvant, but there is a growing body of literature,” he concluded. “Our prospective clinical trial at this point with interim analysis supports that, but there are some caveats that we need to be aware of and not overpromise what this drug can do for our patients.”—Kanaga Rajan, PhD

    Financial disclosures. Dr. Kahana: Genentech: S,C; Stryker Corp/Medical Division: C.

    Disclosure key. C = Consultant/Advisor; E = Employee; L = Speakers bureau; O = Equity owner; P = Patents/Royalty; S = Grant support.

    Watch a 3-minute interview with Dr. Kahana. In this interview from AAO 2019, Dr. Alon Kahana discusses the use of the hedgehog pathway inhibitor vismodegib (Erivedge) for treating basal cell carcinoma. 

    Read more news from AAO 2019 and the Subspecialty Day meetings.