Phase II, Single-Arm Trial of Induction and Concurrent Vismodegib With Curative-Intent Radiation Therapy for Locally Advanced, Unresectable Basal Cell Carcinoma

Abstract

Purpose: Locally advanced, unresectable basal cell carcinoma (LA BCC) can be treated with radiation therapy (RT), but locoregional control (LRC) rates are unsatisfactory. Vismodegib is a hedgehog pathway inhibitor (HPI) active in BCC that may radiosensitize BCC. We evaluated the combination of vismodegib and RT for patients with LA BCC.

Methods: In this multicenter, single-arm, phase II study, patients with unresectable LA BCC received 12 weeks of induction vismodegib, followed by 7 weeks of concurrent vismodegib and RT. The primary end point was LRC rate at 1 year after the end of treatment. Secondary end points included objective response, progression-free survival (PFS), overall survival (OS), safety, and patient-reported quality of life (PRQOL).

Results: Twenty-four patients received vismodegib; five were unable to complete 12 weeks of induction therapy. LRC was achieved in 91% (95% CI, 68 to 98) of patients at 1 year. The response rate was 63% (95% CI, 38 to 84) after induction vismodegib and 83% (95% CI, 59 to 96) after concurrent vismodegib and RT. With a median follow-up of 5.7 years, 1-year PFS and OS rates were 100% and 96%, and at 5 years PFS and OS rates were 78% and 83%, respectively. Distant metastasis or BCC-related death has not been observed. The most frequent treatment-related adverse events (AEs) were dysgeusia, fatigue, and myalgias occurring in 83%, 75%, and 75% of patients. No grade 4 to 5 treatment-related AEs occurred. PRQOL demonstrated clinically meaningful improvements in all subscales, with emotions and functioning improvements persisting for a year after the end of treatment.

Conclusion: In patients with unresectable LA BCC, the combination of vismodegib and RT yielded high rates of LRC and PFS and durable improvements in PRQOL.

Figure 1.

CONSORT.

Figure 2.

Response after 12-14 weeks of induction vismodegib (n=19), 3 months after 7 weeks of concurrent vismodegib and radiotherapy (n=18), and 1 year after 7 weeks of concurrent vismodegib and radiotherapy (n=18). *Represents 5 patients that were not evaluable for response; ↑ represents a patient that died after concurrent vismodegib and RT.

Figure 3.

Kaplan-Meier estimates of (A) progression-free and (B) overall survival with estimated 95% simultaneous confidence intervals (dotted lines).

Figure 3.

Kaplan-Meier estimates of (A) progression-free and (B) overall survival with estimated 95% simultaneous confidence intervals (dotted lines).

Figure 4.

Patient-reported quality of life according to the median Skindex-16 subscale and composite scores prior to, during, and after treatment.

Figure 5.

Example of clinical response to treatment; prior to treatment (A), at the end of induction vismodegib (B), at the end of concurrent vismodegib and RT (C) and 3 years after completing concurrent vismodegib and RT (D).