Hedgehog switching helps BCC patients stay on therapy

Skin cancers

22 Nov 2019

Two Australian case studies have highlighted the advantage of switching between the two available hedgehog signalling pathway inhibitors in order to minimise drug-related adverse effects.

Writing in the Australasian Journal of Dermatology, Dr Matthew Gibson and Professor Dedee Murrell said side effects were common including muscle spasms, alopecia, dysgeusia and weight loss. 

And studies have shown that treatment discontinuation rates were as high as 21% with vismodegib and 30% with sonidegib. 

However as both drugs are PBS-listed for patients with locally advanced or metastatic BCC who are inappropriate for surgery or curative radiotherapy, switching was a viable option. 

In the case of a 74 year-old male with multiple laBCCs on the scalp, vismodegib treatment was effective but lead to debilitating muscle cramps and dysgeusia. On ceasing treatment, the BCCs recurred. 

Further treatment with sonidegib improved his skin lesions without reported side effects.

Similarly, a 46 year-old female was treated effectively with vismodegib for multiple laBCCs on her forehead. However when she discontinued the drug due to intractable cramps and nausea, the lesions recurred.  

A switch to sonidegib was effective within six months and side effects, while still present, were less severe. 

The Letter to the Editor said there is little evidence for how to predict individual treatment response or tolerability. 

“In our two patients, changing hedgehog inhibitors led to a reduction in side effects allowing both to continue treatment. Both drugs were effective at treating their laBCCs.”

“The PBS allows clinicians to swap patients from one hedgehog inhibitor to the other if efficacy is demonstrated but tolerability is not, just as psoriasis patients are able to switch between biologics.”

“Given the paucity of other treatment options for laBCC and mBCC, we argue that clinicians should be aware of and utilise this provision.”

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