Addition of Vismodegib to Radiation Therapy Shows Promise Among Patients With Basal Cell Carcinoma

Results from a prospective, phase 2 study found the addition of induction and concurrent vismodegib, a Hedgehog pathway inhibitor, to radiation therapy was a safe and effective therapeutic option for patients with locally advanced, unresectable basal cell carcinoma. 

“Locally advanced, unresectable basal cell carcinoma can be treated with radiation therapy, but locoregional control rates are unsatisfactory,” stated Christopher A. Barker, MD, Memorial Sloan Kettering Cancer Center, New York, New York, and coauthors. “Preclinical studies suggest that Hedgehog pathway inhibition may render cancer cells more sensitive to the cytotoxic effects of ionizing [radiation therapy].” 

In this single-arm, open-label study, 19 patients with locally advanced, unresectable basal cell carcinoma underwent 12 weeks of induction vismodegib (150 mg once daily) followed by 7 weeks of concurrent vismodegib and radiation therapy (66 to 70 Gy in 33 to 35 fractions) for a maximum of 21 weeks or until disease progression, unacceptable toxicity, or patient withdrawal. The primary end point was 12-month locoregional control (LRC) rate. Secondary end points included 12-month response, progression-free survival (PFS), and overall survival (OS) rates. Additional end points included 5-year PFS and OS rates, safety, and patient-reported quality of life outcomes. 

At 12-month post treatment follow-up, 91% of patients achieved locoregional control. Response rate was 63% after induction vismodegib and 83% after concurrent vismodegib and radiation therapy. PFS rate was 100% and OS rate was 96%. At an additional follow-up of 5.7 years, the PFS rate was 78% and OS rate was 83%. The most frequent treatment-related adverse events included dysgeusia, fatigue, and myalgias. No grade 4 to 5 adverse events were reported. On the Skindex-16 emotions and functioning subscales, patient-reported quality of life scores improved by a median of 10 points in all subscales. Study authors noted that 21% of patients were unable to tolerate vismodegib, but that all patients who started the concurrent vismodegib and radiation therapy regiment were able to complete the course, “suggesting that vismodegib does not increase the toxicity of [radiation therapy] or compromise concurrent [radiation therapy] delivery.”

“These results provide an important benchmark establishing the safety and efficacy of this combined-modality approach,” concluded Dr Barker et al. They noted, “Compared with similar population treated with RT alone, these data suggest that adding vismodegib to [radiation therapy] improves outcomes.”

“This regimen should be considered as a therapeutic option,” added Journal of Clinical Oncology associate editor Maura L. Gillison, MD, PhD, MD Anderson Cancer Center, Houston, Texas. 

Source:

Barker CA, Dufault S, Aaron ST, et al. Phase II, single-arm trial of induction and concurrent vismodegib with curative-intent radiation therapy for locally advanced, unresectable basal cell carcinoma. J Clin Oncol. Published online: April 17, 2024. doi:10.1200/JCO.23.01708