Treating Locally Advanced Basal Cell Carcinoma

Evan Lipson, MD, and Megan Schollenberger, CRNP, both from Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, discuss a patient case of recurrent, locally advanced basal cell carcinoma of the left nasal ala and medial canthus, following the patient through multiple lines of therapy.

Transcript:

Dr Evan Lipson: Hello. I'm Dr. Evan Lipson, associate professor of medical oncology at Johns Hopkins.

Megan Schollenberger: I'm Megan Schollenberger, nurse practitioner at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. Together, Dr. Lipson and I treat patients with advanced and high risk skin cancers. Today, we're going to focus on the therapy landscape for patients with advanced basal cell carcinoma.

Dr Lipson: Basal cell carcinoma is the most common human cancer. In the vast majority of cases, BCC is cured by locally directed therapy, such as Mohs or other forms of peripheral and deep en face margin assessment. However, a small percentage of patients develop locally advanced, surgically unresectable disease. For some of these patients, radiotherapy can successfully control cancer growth. When tumors progress through radiotherapy and for patients with BCC that has metastasized to distance sites, we pursue systemic treatment.

Megan Schollenberger: In most cases, we prescribe vismodegib or sonidegib as frontline standard of care therapy. These are oral drugs that target the hedgehog signaling pathway, which is a driver of most basal cell carcinomas. Although we often use them interchangeably, the FDA approvals for vismo and soni are slightly different. Vismo and soni both have approvals in the locally advanced setting. Vismo also has approval in the metastatic setting. Vismo can be taken with or without food, while soni should be taken on an empty stomach. Soni is also metabolized via the CYP3A4, so we avoid drugs that induce or inhibit CYP3A. We monitor serum creatine kinase, and creatinine levels prior to initiating therapy, and periodically thereafter in patients taking sonidegib.

Dr Lipson: The efficacy of the hedgehog pathway inhibitors is illustrated by results from the BOLT study, a multicenter phase two 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. Similarly, the ERIVANCE study was an international phase two trial testing vismodegib in about a 100 patients with either metastatic or locally advanced BCC. Overall response rates were 30% in the metastatic cohort, and 43% in the locally advanced patients. The median duration of response was 7.6 months in both arms of the trial

Megan Schollenberger: Common side effects of this drug class include muscle spasms, fatigue, hair loss, distortion of the sense of taste, and gastrointestinal disorders, such as nausea, vomiting, diarrhea, and constipation. Additionally, hedgehog pathway inhibitors are potent to [inaudible 00:03:01]. We counsel patients about the potential dangers of exposure to women of childbearing potential. We also advise that patients abstain from donating blood or blood products before, during, and for 24 months after drug administration.

Dr Lipson: We generally continue therapy until we see evidence of disease progression or unacceptable toxicity. While the drug-related adverse events are typically not life threatening, side effects are a common reason for drug discontinuation due to their negative impact on the patient's quality of life. In many cases, we'll hold therapy for several weeks at a time to allow for side effects-associated symptoms to subside.

Megan Schollenberger: In patients who receive hedgehog pathway inhibitor therapy and experience tumor progression or intolerable toxicity, and in patients for whom hedgehog pathway inhibitor therapy is not appropriate, we often administer cemiplimab, an anti PD-1 agent. Cemiplimab promotes the activation and proliferation of patient's T cells with the goal of triggering immune mediated tumor cell destruction.

Dr Lipson: In a study involving 84 patients with locally advanced BCC, cemiplimab demonstrated an overall response rate of 31%. The safety profile associated with cemiplimab is consistent with previous studies of anti-PD-1 monotherapy. With a median duration follow up 15 months, the median duration of response had not been reached.

Megan Schollenberger: Here at John's Hopkins, we're investigating the use of anti PD-1 in the frontline setting for patients with advanced BCC. We're also testing the safety and efficacy of additional immune checkpoint inhibitors, including anti-LAG-3 and anti-CTLA-4 in patients for whom anti-PD-1 alone is insufficient.

Dr Lipson: We're looking forward to presenting results from this ongoing study in the fall of 2022. We hope you enjoyed our discussion today about treatment options for patients with advanced basal cell carcinoma. Thanks for watching.