Original article
An investigator-initiated open-label clinical trial of vismodegib as a neoadjuvant to surgery for high-risk basal cell carcinoma

The interim analysis of this research was presented at the “Late Breaking Research” session at the American Academy of Dermatology March 2013 Annual Meeting, Miami, FL.
https://doi.org/10.1016/j.jaad.2014.05.020Get rights and content

Background

Vismodegib is an oral hedgehog-pathway inhibitor approved for advanced basal cell carcinoma (BCC). Although most BCCs are amenable to surgery, excision of large tumors in aesthetically sensitive sites may compromise function or cosmesis.

Objective

We sought to evaluate the reduction in BCC surgical defect area after 3 to 6 months of neoadjuvant vismodegib.

Methods

This was an open-label, single-arm intervention trial with a primary outcome of change in target-tumor surgical defect area pre- and post-vismodegib (150 mg/d). Secondary outcomes were change in tumor area and tolerability.

Results

Eleven of 15 enrolled patients, aged 39 to 100 years, completed the trial. Thirteen target tumors were excised after a mean of 4 ± 2 months of vismodegib. In all, 29% (4 of 14 patients) could not complete more than 3 months because of vismodegib-related side effects. The mean baseline target-tumor diameter was 3.2 cm, and 10 of 13 tumors occurred on the face. Overall, vismodegib reduced the surgical defect area by 27% (95% confidence interval –45.7% to –7.9%; P = .006) from baseline. Vismodegib was not effective in patients who received less than 3 months. Over a mean follow-up of 11.5 (range 4-21) months for all tumors, only 1 tumor recurred at 17 months post-Mohs micrographic surgery.

Limitations

Short follow-up time and no placebo control are limitations.

Conclusion

Neoadjuvant vismodegib appears to reduce surgical defect area when taken for 3 months or longer for nonrecurrent BCCs in functionally sensitive locations. Further studies with larger sample sizes and long-term follow-up are warranted.

Section snippets

Methods

All patients meeting study inclusion criteria were offered participation (N = 17). We enrolled 15 patients over 18 years of age with at least 1 biopsy-confirmed BCC of any histologic subtype, more than 5 mm in diameter, eligible for surgical removal, and who agreed to participate in an investigator-initiated, open-label, single-arm intervention trial (NCT01631331) from April 2012 to July 2013 at a single institution. Patients with previously treated/recurrent BCCs were also eligible. We

Patients

We enrolled 15 patients; 11 patients completed the trial and had their target BCCs surgically excised (10 by Mohs and 1 by standard excision). One patient was lost to follow-up, 2 patients withdrew from the trial because of vismodegib-related side effects (elevated creatine phosphokinase, fatigue), and 1 patient withdrew because of unrelated adverse events (ventriculoperitoneal shunt obstruction) (Fig 1 [CONSORT diagram]). The mean age of the 11 patients was 59 (range 39-100) years (Table I).

Discussion

Neoadjuvant treatment with vismodegib for an average of 4 months before surgery reduced tumor area and surgical defect size.10 This reduction was seen primarily in nonrecurrent tumors. Efficacy appears to be duration dependent as a minimum of 3 months of vismodegib was required. Hair loss, muscle cramps, and dysgeusia cannot be avoided even with short-term use. Clinical appearance of tumors after vismodegib was variable and did not predict histologic cure.

To date, there have been no clinical

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Dr Ally and Dr Aasi contributed equally to this work.

This investigator-initiated trial was supported in part by a Damon Runyon Cancer Research Foundation Clinical Investigator Award (CI-54-11 to Dr Tang).

Disclosure: Drs Tang, Chang, and Oro have been investigators in studies sponsored by Genentech. Dr Oro has also been an investigator in studies sponsored by Infinity and Novartis and Dr Chang is also a clinical investigator for studies sponsored by Novartis and Lilly. Drs Ally, Aasi, Wysong, and Kim; Ms Teng; Mr Anderson; and Ms Bailey-Healy have no conflicts of interest to declare.

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