Large Trial Confirms Vismodegib Benefit in Basal Cell Carcinoma

Nicole Basset-Seguin, MD, PhD

The hedgehog inhibitor vismodegib (Erivedge) had an estimated disease control rate of 92.9% in the STEVIE trial, the largest ever study conducted in advanced basal cell carcinoma, according to results presented at the 2016 ASCO Annual Meeting.

“The STEVIE study, which included 1215 patients, confirms the high antitumoral efficacy of vismodegib in difficult to treat patients with advanced basal cell carcinoma, and there were no additional or life threatening side effects compared to previously studies,” study author Nicole Basset-Seguin, MD, PhD, Centre d'Oncodermatologie, Hôpital Saint-Louis, Paris, France, said in an interview with OncLive.

The international, single-arm, open-label STEVIE trial included 1215 patients with metastatic (n = 96) or locally advanced (n = 1119) basal cell carcinoma. Patients were enrolled between June 30, 2011, and September 2, 2014, at 167 sites across 36 countries.

The median patient age was 72 years (range, 18-101) and 57.1% (n = 694) of patients were male. The ECOG performance status was 0 for 57.7% of patients (n = 701), with the remaining patients having a performance status of 1 (n = 358; 29.5%) or 2 (n = 153; 12.6%). Approximately 70% of patients had not received prior radiotherapy.

Patients received 150 mg/day of vismodegib orally until disease progression, unacceptable toxicity, or withdrawal from the study. Safety was the primary outcome measure. Efficacy and quality of life variables were secondary endpoints.

The analysis reported at ASCO had a data cutoff of March 16, 2015. At the cutoff, the median duration of treatment was 263 days (8.6 months) and 12% of patients (n = 147) were still receiving treatment.

Among the 88% (n = 1068) of patients who discontinued treatment, the primary reasons included treatment-related adverse events (AEs; n = 349; 28.7%), disease progression (n = 189; 15.6%), patient request (n = 113; 9.3%), physician decision (n = 76; 6.3%), death (n = 37; 3%), loss to follow-up (n = 21; 1.7%), or other reasons (n = 283; 23.3%).

Efficacy outcomes were determined for 1161 patients who had measurable disease at baseline. The best overall response rate was 66.2% (n = 769; 95% CI, 63.43-68.96). The disease control rate of 92.9% included a complete response (CR) rate of 31.4% (n = 364), a partial response (PR) rate of 34.9% (n = 405), and a stable disease rate of 26.6% (n = 309). The median time to response was 3.7 months (95% CI, 3.5-3.7) and the median duration of response was 22.7 months (95% CI, 20.3-24.8). The progressive disease rate was 2.6% (n = 30).

The median PFS was 22.1 months (95% CI, 20.3-24.7). The overall survival data were not yet mature at the time of the analysis.

Safety outcomes in the trial were consistent with previously reported AE data for vismodegib. Basset-Seguin and her fellow researchers also noted in their ASCO poster that, “Long-term exposure was not associated with worsening of severity or frequency of treatment-related AEs.”

All-grade treatment-related AEs occurred in 98% (n = 1192) of patients. The most common all-grade AEs were muscle spasm (66.4%), alopecia (61.5%), dysgeusia (54.6%), weight decrease (40.6%), and decreased appetite (24.9%). Over half (54%) of the AEs were mild to moderate.

Grade 3 AEs included muscle spasm (7.7%), alopecia (1.2%), dysgeusia (2.1%), weight decrease (3.9%), decreased appetite (1.6%), asthenia (1.8%), nausea (0.3%), ageusia (1.2%), fatigue (1.6%), diarrhea (0.7%), and arthralgia (0.3%). Grade 4 AEs occurring in 1 patient each included muscle spasm, alopecia, dysgeusia, weight decrease, asthenia, ageusia, and fatigue.

Serious treatment-related AEs occurred in 289 patients (24%) and included pneumonia (1.5%), cutaneous squamous cell carcinoma (1%), and general physical health deterioration (1%).

There were 110 patient deaths (9.1%) on study or during follow-up, 5.8% (n = 71) of which were related to AEs. Twenty-seven deaths (2.2%) were attributed to progressive disease.

Treatment-related AEs occurred in 46 patients (3.8%); however, with 7 of these deaths, the investigator noted that there were comorbidities/risk factors confounding the cause of death.

The FDA approved vismodegib in January 2012 for use as a treatment for patients with advanced basal cell carcinoma who have either metastatic disease or locally advanced disease that cannot be treated with surgery or radiation. The approval was based on a study involving 96 patients with locally advanced or metastatic basal cell carcinoma. In the metastatic cohort, 30% of patients had a partial response, and in the group of patients with locally advanced disease, 43% had a PR or CR.

Hansson J, Hauschild A, Kunstfeld R, et al. Vismodegib (VISMO), a hedgehog pathway inhibitor (HPI), in advanced basal cell carcinoma (aBCC): STEVIE study primary analysis in 1215 patients (pts). J Clin Oncol 34, 2016 (suppl; abstr 9532).