Case Presentation: A Woman With Locally Advanced Basal Cell Carcinoma Case Presentation

A 95-year-old woman with mild dementia presented to your medical oncology clinic with multiple recurrent, locally-advanced basal cell carcinoma of the left nasal ala and medial canthus. The tumor had first appeared 10 years earlier. Despite having undergone multiple surgical resections and radiation therapy, the basal cell carcinoma (BCC) recurred. The patient was evaluated by your multidisciplinary team and was decided not to be a candidate for further surgery or radiation therapy.

You prescribed vismodegib, an oral drug that targets the hedgehog signaling pathway, which is a driver of most basal cell carcinomas. Another option would have been sonidegib, which is also a hedgehog pathway inhibitor. Although the 2 medications have not been compared head-to-head, information gleaned from cross trial comparisons suggests that they have approximately equivalent efficacy and tolerability.

The efficacy of hedgehog inhibitors is illustrated by results from the BOLT study, a multicenter, randomized, double-blind, phase 2 trial evaluating daily administration of sonidegib in 194 patients with locally-advanced BCC. The objective response rate was 56% with a median duration of response of 26.1 months.

The patient started vismodegib, and her tumor regression was evident by about 6 weeks. She reported mild taste changes, but otherwise tolerated the medication well. About 3 months into therapy, the patient’s tumor continued to regress, though her dysgeusia had worsened considerably. She no longer enjoyed eating, which was a major source of pleasure for this patient.  Given these worsening adverse effects, the patient’s care team decided to pause the use of vismodegib. As is often the case in these instances, the patient’s dysgeusia took several months to decrease in severity. Over that period, her BCC remained stable, and the dysgeusia eventually decreased in severity about 9 months after the discontinuation of vismodegib. You discussed the possibility of restarting vismodegib, however the patient declined, given concerns about toxicity.

It is important to note that toxicity is a common reason for discontinuation of hedgehog pathway inhibitor therapy. The drug-related adverse effects are typically not life-threatening, but they often have a negative impact on a patient’s day-to-day life.

You recommended cemiplimab as second-line medical therapy. Cemiplimab is a PD-1-blocking antibody (anti-PD-1), which was approved by the FDA for patients with advanced basal cell carcinoma who were previously treated with a hedgehog pathway inhibitor, or for whom a hedgehog pathway inhibitor is not appropriate.

You discussed the potential benefits of this therapy, including a 29% response rate in a study involving 84 patients with locally-advanced BCC. Of the 24 patients whose tumors responded to cemiplimab, almost 80% of those responses lasted at least 6 months. We also discussed the potential immune-related toxicities associated with anti-PD-1. An issue that arose during your discussions with your 96-year-old patient and her family members was whether cemiplimab is well-tolerated in older adults. Research shows the efficacy and safety profiles of anti-PD-1 in the older-adult population mirrors those seen in younger patients. Investigators from the Melanoma Institute of Australia reported similar findings from their cohort of more than 200 patients with melanoma.

Your patient began therapy with cemiplimab and tolerated it well. About 5 months into therapy, her BCC began to regress and she became better able to open her left eye. After about 18 months of therapy, cemiplimab was discontinued in the setting of a complete response. You discussed with the patient and her family members that an ongoing anti-tumor response off therapy is not uncommon after a patient has experienced tumor regression to anti-PD-1.