Cemiplimab (Libtayo) is emerging as a valuable treatment option for patients with advanced basal cell carcinoma (BCC) who have previously been treated with or are ineligible for hedgehog pathway inhibitors (HHIs). The phase 2 Study 1620 demonstrated promising results, offering a new avenue for patients with limited therapeutic options.
Efficacy of Cemiplimab in Advanced BCC
The Study 1620, a phase 2 trial, evaluated the efficacy and safety of cemiplimab in patients with metastatic or locally advanced BCC. Patients were administered 350 mg of cemiplimab every three weeks. The primary endpoint was the overall response rate (ORR) as assessed by independent central review (ICR). Key secondary endpoints included duration of response, progression-free survival (PFS), overall survival (OS), and safety.
The ORR by ICR was 22%, while investigator assessment showed an ORR of 26%. The disease control rate exceeded 30%, with many patients achieving stable disease or partial responses. The median PFS was 10 months, and the 12-month OS rate was 83%. These results underscore the potential of cemiplimab to provide meaningful clinical benefit in this patient population.
Tolerability and Adverse Events
HHIs like vismodegib (Erivedge) and sonidegib (Odomzo) are often the first line of treatment for advanced BCC. However, their use is frequently limited by significant adverse events (AEs). Common AEs include nausea, vomiting, diarrhea, constipation, fatigue, taste changes, weight loss, muscle spasms, and arthralgias. According to Dr. Jennifer L. Atlas, these side effects, particularly muscle spasms and arthralgias, are among the most common reasons for HHI discontinuation.
In contrast, cemiplimab's AE profile, while including fatigue and gastrointestinal issues, also presented hypertension as a notable concern, with a grade 3 hypertension rate of 11% in the Study 1620. Despite these challenges, the overall tolerability of cemiplimab allows many patients to continue treatment and achieve clinical benefits.
Patient Selection and Treatment Considerations
Selecting appropriate patients for cemiplimab therapy involves careful consideration of their prior treatment history and overall health. Patients eligible for the Study 1620 had a diagnosis of invasive BCC and had either progressed on or were intolerant to an HHI, or had no better than stable disease after nine months of HHI therapy. Exclusion criteria included ongoing autoimmune diseases requiring immune suppression, prior PD-1 or PD-L1 therapy, or concurrent malignancy other than basal cell carcinoma or another nonmelanoma skin cancer.
Dr. Atlas emphasized the importance of managing patient expectations, noting that responses to cemiplimab in BCC may take longer compared to other cutaneous malignancies, typically averaging between three and four months.
The Role of Immunotherapy in BCC Treatment
The introduction of immunotherapy with cemiplimab represents a significant advancement in the treatment of advanced BCC. For patients who have exhausted HHI options or cannot tolerate their side effects, cemiplimab offers a valuable alternative with a manageable safety profile and the potential for durable responses. The data from Study 1620 supports the use of cemiplimab as a second-line therapy, providing hope and improved outcomes for patients with this challenging disease.
