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Intermittent Vismodegib Regimens in Patients With Multiple Basal Cell Carcinomas

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Key Points

  • Two intermittent dosing regimens of vismodegib resulted in similar reduction in the number of basal cell carcinomas in patients with multiple lesions.
  • A greater reduction was observed with the 12/8/12 regimen in analysis excluding patients with basal cell nevus syndrome.

In a phase II trial reported in The Lancet Oncology, Dréno et al 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.

Study Details

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 at least 6 clinically evident basal cell carcinomas, including patients with basal cell nevus syndrome, were randomized between April 2013 and April 2014 to receive the following: vismodegib at 150 mg daily for 12 weeks followed by 3 rounds of 8 weeks of placebo daily and then 150 mg of vismodegib daily for 12 weeks (12/8/12 group; n = 116) or vismodegib at 150 mg daily for 24 weeks followed by 3 rounds of 8 weeks of placebo daily and then vismodegib at 150 mg daily 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; P = .24 for model not adjusting for stratification factors). 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%). Serious adverse events occurred in 19% vs 17% of patients.

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%); 1 death in the 12/8/12 group, due to pulmonary embolism, was considered possibly related to vismodegib treatment.

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. Further study is warranted.”

The study was funded by F. Hoffmann-La Roche.

Brigitte Dréno, MD, of Nantes University, Nantes, France, is the corresponding author of The Lancet Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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