Phase II Trial Shows Promise for Combining Vismodegib and RT in Advanced BCC

Presenting author:
Christopher Barker, MD

By Nancy Y. Lee, MD, FASTRO, Memorial Sloan-Kettering Cancer Center

For many years, radiation therapy (RT) has been the main treatment for unresectable, locally advanced basal cell carcinoma (BCC). Patients whose tumors are not controlled can experience devastating cancer-related problems such as bleeding and malodor from fungating tumors that are locally destructive. This phase II single arm trial of induction and concurrent vismodegib with RT for locally advanced unresectable BCC of the head and neck reported by Christopher Barker, MD, Director of Skin Cancer and Melanoma Service in the Department of Radiation Oncology at the Memorial Sloan Kettering Cancer Center, has shown tremendous promise.

The hypothesis of this trial sprang from observations that vismodegib can radiosensitize cancer cells in preclinical models and hence the rationale for combining vismodegib and RT with the goal of yielding higher locoregional control rates compared to historically reported rates with RT or vismodegib alone. Recall that the hedgehog pathway is implicated in the oncogenesis of BCC with mutations in the receptor of sonic hedgehog. By targeting the hedgehog pathway, vismodegib can suppress tumor growth.

This trial included patients with BCC ≥2 cm in size and/or with nodal metastasis but without distant metastasis. Patients received 12 weeks of induction vismodegib (150 mg orally once daily) followed by seven weeks of concurrent vismodegib and RT to 66-70 Gy in 33-35 fractions. The combination was tolerable with the most frequent adverse events being dysgeusia, fatigue and myalgias. With median follow up of 5.7 years, one-year progression free survival (PFS) and overall survival (OS) rates were 100% and 96%, and at five-year PFS and OS rates 78% and 83%. Distant metastasis or BCC-related death has not been observed. The one-year locoregional control was excellent at 91% (95% CI 68-98%). Response rate was 63% (95% CI 38-84%) after induction vismodegib and 83% (95% CI 59-96%) following concurrent vismodegib and RT.

This trial, designed by Sue Yom, MD, PhD, FASTRO, Professor of Radiation Oncology and Otolaryngology-Head and Neck Surgery at the University of California, San Francisco, is remarkable for several reasons. First, it represents the first prospective clinical trial of RT for unresectable BCC, the most common cancer in humans.1 Second, this is one of the few studies of curative intent RT and an oral molecularly targeted cancer therapy. Third, it demonstrates that appropriate rationale can lead to successful combined modality therapy studies. Finally, it demonstrated high rates of disease control, with mature follow up. Taken together, patients with unresectable, locally advanced BCC should be considered for treatment with vismodegib and RT.

The authors are to be congratulated for their tremendous work that could set a new standard for these patients. The next obvious question is whether this combination can be effective for patients with resectable BCC to improve cosmetic outcomes when complex reconstructive surgery would be otherwise necessary.

Abstract 9 - A Phase II Single Arm Trial of Induction and Concurrent Vismodegib with Curative Intent Radiation Therapy for Locally Advanced, Unresectable Basal Cell Carcinoma of the Head and Neck was presented during the K. Kian Ang, MD, PhD, FASTRO, Commemorative Plenary Session at the 2024 Multidisciplinary Head and Neck Cancers Symposium on February 29, 2024.

1. Global Burden of Disease Cancer Collaboration, Fitzmaurice C, Abate D, et al. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017: A Systematic Analysis for the Global Burden of Disease Study [published correction appears in JAMA Oncol. 2020 Mar 1;6(3):444] [published correction appears in JAMA Oncol. 2020 May 1;6(5):789] [published correction appears in JAMA Oncol. 2021 Mar 1;7(3):466]. JAMA Oncol. 2019;5(12):1749-1768.




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