Sustaining Long-Term Hedgehog Inhibitor Therapy in Surgery-Refractory BCC Patients

Continuing the first case, "Sustaining Long-Term Hedgehog Inhibitor Therapy in Surgery-Refractory BCC Patients" examines long-term efficacy data and the practical work of keeping patients on treatment.

Dr. Singh notes that not every patient achieves a complete response, so long-term data matter. He states that sonidegib is the only hedgehog inhibitor with a median duration of response exceeding 2 years, possibly reflecting its high volume of distribution. He cautions that the BOLT and ERIVANCE BCC trials were not head-to-head.

He does point out that the vismodegib trial assessed response in one dimension. Tumors do not grow in one dimension, he argues, and length and width both drive surgical morbidity. At the 42-month final BOLT analysis, only 8% of the 200-mg cohort and 3% of the 800-mg cohort remained on treatment. At 200 mg, objective response rates were 56% in locally advanced and 8% in metastatic disease, with no new safety signals.

Dr. Singh describes himself as a purist about trial data. He permits drug holidays of up to 21 days, as allowed in BOLT, but does not use altered dosing schedules. He acknowledges that many clinicians report good outcomes with nonstandard dosing.

He monitors creatine kinase, renal function, a CBC, and a CMP at baseline, weekly for 2 months, and then every 4 weeks. Abnormalities or worsening symptoms prompt weekly checks until resolution.

He then outlines supportive strategies. For alopecia, oral minoxidil, oral finasteride, and spironolactone may help in appropriate patients. Nausea is addressed with behavioral therapy, relaxation techniques, and pharmacologic options such as scopolamine. Muscle spasms, more frequent after age 70, are managed with hydration, stretching, heat, and vitamin B complex, with cardiology input on amlodipine or diltiazem.

For taste changes, he encourages patients to try new foods, and naturopathic colleagues may add zinc. Fatigue prompts anemia screening, physical activity, and management of pain, insomnia, or depression, with methylphenidate considered by psychiatry when necessary.

Next, "Case 2: Evaluating a Surgery-Averse Patient With Recurrent Nasal BCC" introduces a second patient whose love of cooking shapes the choice between the two agents.