In a phase II trial reported in The Lancet Oncology, Brigitte Dréno, MD, of Nantes University, Nantes, France, and colleagues found that two long-term intermittent vismodegib (Erivedge) dosing regimens provided a similar reduction in the number of clinically significant basal cell carcinomas among patients with multiple lesions.
In the double-blind trial, 229 adult patients from 52 sites in 10 countries in North and South America and Europe who had at least 1 histopathologically confirmed and at least 6 clinically evident basal cell carcinomas, were randomized between April 2013 and April 2014 to receive vismodegib at 150 mg/d for 12 weeks followed by 3 rounds of 8 weeks of placebo daily and then 150 mg/d of vismodegib for 12 weeks (12/8/12 group; n = 116) or vismodegib at 150 mg/d for 24 weeks followed by 3 rounds of 8 weeks of placebo daily and then vismodegib at 150 mg/d for 8 weeks (24/8/8 group; n = 113).
The primary endpoint was percentage reduction in the number of clinically evident basal cell carcinomas between baseline and week 73 in the intent-to-treat population. All patients but one were immunocompetent. Basal cell nevus syndrome was present in 38% of the 12/8/12 group and 36% of the 24/8/8 group.
Reduction in Lesions
The mean number of basal cell carcinoma lesions at week 73 was reduced from baseline by 62.7% in the 12/8/12 group vs 54.0% in the 24/8/8 group (P = .21 for model adjusting for stratification factors of diagnosis of basal cell nevus syndrome, geographic region, and immunosuppression status). A greater reduction in the size of 3 target lesions was observed in the 12/8/12 group (82.9% vs 68.8%, P = .015).
Among patients with basal cell nevus syndrome, there was no significant difference between the two groups in mean relative reduction in the number of basal cell carcinomas (difference = 2.1%, P = .89 in adjusted model). Among those without basal cell nevus syndrome, the mean relative reduction was greater in the 12/8/12 group (difference = –15.4%, P =.025 in the adjusted model).
Adverse Events
The most common grade ≥ 3 treatment-related adverse events were muscle spasms (4% in 12/8/12 group vs 11% in 24/8/8 group), increased blood creatine phosphokinase (1% vs 4%), and hypophosphatemia (0% vs 3%).
Treatment was discontinued due to adverse events in 19.8% vs 26.6%, with the most common adverse events leading to discontinuation of treatment consisting of muscle spasm (6% vs 12%) and dysgeusia (4% vs 8%). Adverse events led to death in 4 patients (2%).
The investigators concluded: “Both intermittent dosing schedules of vismodegib seemed to show good activity in long-term regimens in patients with multiple basal-cell carcinomas.”
The study was funded by F. Hoffmann-La Roche.
