Hedgehog Pathway Inhibitor Use Supported For Advanced BCC

Vismodegib and sonidegib increase the treatment options for patients with inoperable, advanced basal cell carcinoma

medwireNews: Results from the STEVIE and BOLT clinical trials lend support to the use of hedgehog pathway inhibitors for patients with advanced basal cell carcinoma (BCC).

The studies, both of which are published in The Lancet Oncology, were conducted in patients with locally advanced or metastatic disease who were not eligible for curative surgery or radiation.

The pre-planned analysis of the multicentre, open-label STEVIE trial of vismodegib 150 mg/day gave an overall response rate of 66.7% for the 453 patients with locally advanced disease, including 153 complete and 149 partial responses.

And the overall response rate was 37.9% for the 29 patients with metastatic disease, including two complete and nine partial responses, report Johan Hansson, from Karolinska University Hospital in Stockholm, Sweden, and co-authors.

The safety profile of vismodegib was “consistent” with previous reports of the agent, the researchers note, with 98% of patients experiencing side effects, most commonly muscle spasms (64%), alopecia (62%), dysgeusia (54%), weight loss (33%), asthenia (28%), decreased appetite (25%), ageusia (22%), diarrhoea (17%), nausea (16%) and fatigue (16%).

Although most adverse events were grade 1 or 2, 22% of patients had grade 3 or more severe events and 21 of the 31 deaths were related to the drug.

Nevertheless, the researchers describe vismodegib as “tolerable in a patient population that is representative of patients treated in routine clinical practice”, noting that treatment was discontinued due to adverse events in 36% and on patient request in just 10%.

“Our results show that treatment with vismodegib adds a novel therapeutic modality from which patients with advanced basal cell carcinoma can benefit substantially”, conclude Johan Hansson et al.

Meanwhile, central review of data from the BOLT study of sonidegib gave an objective response rate of 38% for the 93 patients with locally advanced disease given 800 mg/day and 17% for the 23 patients with metastatic disease. The rate was 43% for the 42 patients given sonidegib 200 mg/day and 15% for the 13 with metastatic disease.

Of note, between 54% and 74% of patients given sonidegib were free from progression at 12 months, the randomised, multicentre study indicated.

Patients in the 200 mg/day group were less likely than those given 800 mg/day to require a dose interruption or reduction (32 vs 60%) or have their treatment discontinued (22 vs 36%). The most common grade 3 or 4 adverse events were elevated creatine and lipase, with serious events occurring in 14% and 30% of the low and high dose groups, respectively.

“Limited quality-of-life data exist for patients with advanced basal cell carcinoma, but it is clear that many patients have physical and emotional distress”, write Michael Migden, from the University of Texas MD Anderson Cancer Center in Houston, USA, and BOLT co-authors.

“Treatment with sonidegib resulted in preservation of or improvement in quality of life for most patients”, they emphasise.

“Together, our data show a positive benefit-to-risk profile with sonidegib, which could be a promising new option for the treatment of patients with advanced basal cell carcinoma.”


Basset-Seguin N, Hauschild A, Grob J-J, et al. Vismodegib in patients with advanced basal cell carcinoma (STEVIE): a pre-planned interim analysis of an international, open-label trial. Lancet Oncol 2015; Advance online publication 13 May. DOI: http://dx.doi.org/10.1016/S1470-2045(15)70198-1

Migden MR, Guminski A, Gutzmer R, et al. Treatment with two different doses of sonidegib in patients with locally advanced or metastatic basal cell carcinoma (BOLT): a multicentre, randomised, double-blind phase 2 trial. Lancet Oncol 2015; Advance online publication 13 May. DOI: http://dx.doi.org/10.1016/S1470-2045(15)70100-2

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