What is the primary treatment for metastatic basal cell cancer?

Primary Treatment for Metastatic Basal Cell Cancer

The primary treatment for metastatic basal cell carcinoma (BCC) is systemic therapy with a hedgehog pathway inhibitor, specifically FDA-approved medications vismodegib or sonidegib, managed by a multidisciplinary tumor board. 1

First-Line Treatment Options

• Whenever possible, nodal or distant metastases should first be evaluated for potential surgical resection with or without radiation therapy 1
• For patients with distant metastases, multidisciplinary consultation is recommended to guide treatment with hedgehog pathway inhibitors 1
• FDA-approved hedgehog pathway inhibitors include:
  • Vismodegib (150 mg orally once daily) 2
  • Sonidegib (200 mg once daily) 1, 3

Evidence for Hedgehog Pathway Inhibitors

• Vismodegib demonstrated an objective response rate of 30-33% in metastatic BCC patients, with a median duration of response of 7.6 months 1
• The majority of patients (73%) experienced tumor shrinkage with vismodegib, though all responses were partial rather than complete 1
• The STEVIE trial showed an overall response rate of 37.9% with vismodegib in metastatic BCC 1
• Sonidegib showed objective response rates of 8-17% in metastatic BCC in the BOLT study with sustained efficacy over 42 months of follow-up 3

Second-Line Options

• If hedgehog pathway inhibitors are not feasible or fail, platinum-based chemotherapy may be considered 1
• Clinical trial enrollment should be considered for patients who have failed first-line therapy 4
• Best supportive and palliative care should be provided to optimize symptom management and maximize quality of life 1

Important Considerations and Monitoring

• Hedgehog pathway inhibitors are associated with significant adverse events:

  • Common side effects include muscle spasms, arthralgias, alopecia, dysgeusia, and weight loss 1
  • In the STEVIE trial, 36% of patients discontinued treatment due to adverse events 1
  • Regular monitoring for side effects, benefit, and compliance is required 4

• Embryo-fetal toxicity is a serious concern:

  • Verify pregnancy status before initiating treatment 2
  • Effective contraception is required during treatment and for 24 months after final dose for females 2
  • Males should use condoms during treatment and for 3 months after the final dose 2

Follow-Up Recommendations

• Close follow-up is essential as 30-50% of BCC patients develop another BCC within 5 years 1
• Complete skin examinations should occur at least every 6-12 months during the first 2 years after treatment 1
• Patients should be educated about sun protection and regular self-examination of the skin 1

Emerging Approaches

• Other hedgehog pathway inhibitors (itraconazole, saridegib) have shown responses in small studies but not in patients previously treated with vismodegib 1
• Research continues on various dosing regimens and combination approaches to improve response rates and address resistance to hedgehog pathway inhibitors 5, 6

Pitfalls to Avoid

• Do not use systemic therapies in place of potentially curative procedures; they require long-term treatment and are not curative 4
• Evaluation by experienced physicians and/or a multidisciplinary tumor board for possible curative surgery with or without radiation is recommended before initiating systemic therapy 4
• Primary and secondary resistance to hedgehog pathway inhibitors can develop, requiring close monitoring and consideration of alternative approaches 4, 5