Patients with locally advanced or metastatic BCC show enduring responses to the hedgehog pathway inhibitor sonidegib, final results from the BOLT study have shown.

But high rates of musculoskeletal side effects and withdrawals from treatment suggest a need to manage patient expectations and use intermittent therapy, say study investigators.

Releasing the final 42-month follow up data for the phase 2 trial of 230 patients that was used to obtain approval of the drug in Australia, the researchers reported objective response rates for the approved 200 mg daily dose of 56% in locally advanced BCC and 8% in metastatic BCC.

At 42 months the disease control rates (DCR) (the sum of complete response, partial response, and stable disease rates) for the 79 patients in the 200mg arm of the trial were 90.9% for locally advanced BCC and  92.3% for metastatic disease. As per previous analyses, response rates were no better with the 800mg dose, which also resulted in higher rates of adverse events.

The median duration of response (DOR) for responders to the 200 mg dose with locally advanced BCC was 26·1 months, and responses lasting six months or longer were seen in 23 of 37 responders.

As expected, the musculoskeletal adverse effects were a major cause of treatment discontinuation, with only 8% of patients remained on 200mg treatment by the 42-month cutoff.

Grade 3–4 adverse events were reported in 32% of patients receiving sonidegib 200 mg and the most common adverse event was muscle spasms, reported in 54% of patients.

The study authors – including  Dr Alex Guminski of the Royal North Shore Hospital, Sydney – said the findings showed that sonidegib had durable effects in advanced BCC, and they suggested the use of intermittent dosing schedules to help patients manage the musculoskeletal adverse effects.

“Real-world treatment plans with sonidegib should include management of adverse events associated with hedgehog pathway inhibitor therapy, as well as patient education plus intermittent therapy, which also may facilitate increased treatment duration, and therefore improve patient benefit,” they wrote.

The results are published in the British Journal of Dermatology.