As reported in The Lancet Oncology by Stratigos et al, findings in a subgroup of a phase II trial have shown that the PD-1 antibody cemiplimab-rwlc produces enduring responses in patients with locally advanced basal cell carcinoma who had progressive disease on or intolerance to prior hedgehog inhibitor (HHI) therapy.

Study findings in the subgroup of patients with locally advanced disease and in a subgroup of patients with metastatic disease supported the February 2021 regular approval of cemiplimab-rwlc for treatment of patients with locally advanced basal cell carcinoma previously treated with a HHI or for whom a HHI is not appropriate, as well as the accelerated approval for treatment of patients with metastatic basal cell carcinoma previously treated with a HHI or for whom a HHI is not appropriate.

Study Details

Eighty-four patients with locally advanced disease from sites in Canada, Europe, and the United States were enrolled in the study between November 2017 and January 2019. Patients were not candidates for further HHI therapy due to progression of disease on or intolerance to previous HHI therapy or having no better than stable disease after 9 months on HHI therapy. Patients received intravenous cemiplimab at 350 mg every 3 weeks for up to 93 weeks or until disease progression or unacceptable toxicity. The primary endpoint was objective response on independent central review.  

Responses

At data cutoff (February 2020), median duration of follow-up was 15 months (interquartile range = 8–18 months). Objective response was observed in 26 (31%, 95% confidence interval [CI] = 21%­–42%) of 84 patients, with complete response in 5 (6%). An additional 41 patients (49%) had stable disease, with disease control observed in 67 patients (80%, 95% CI = 70%–88%). Durable disease control—defined as remaining without progressive disease for at least 182 days—was observed in 50 patients (60%, 95% CI = 48%–70%).

Median time to response was 4.3 months (95% CI = 4.2–7.2 months). Median duration of response was not reached. Observed durations of response at data cutoff ranged from 2 to 21 months, with 79% of responses maintained for ≥ 6 months and 46% for ≥ 12 months. Kaplan-Meier estimates of response duration were 91% (95% CI = 68%–98%) maintained at 6 months and 85% (95% CI = 61%–95%) maintained at 12 months.

The median Kaplan-Meier estimate of progression-free survival was 19 months (95% CI = 9 months–not evaluable), with estimated rates at 6 and 12 months of 76% (95% CI = 65%–84%) and 57% (95% CI = 44%–67%). Median overall survival was not reached at data cutoff (10 events). The Kaplan-Meier estimate of the proportion of patients remaining alive at 2 years was 80% (95% CI = 63%–90%).

Adverse Events

Grade 3 and 4 adverse events occurred in 48% of patients, with the most common being hypertension (5%) and colitis (5%) and fatigue, urinary tract infection, and visual impairment (4% each). Serious adverse events occurred in 35% of patients and were considered treatment-related in 11%; the most common treatment-rated serious adverse events were colitis (4%) and adrenal insufficiency (2%). Treatment-related adverse events led to discontinuation of treatment in 11% of patients, with causes consisting of grade 3 adrenal insufficiency, grade 3 asthenia, grade 3 colitis, grade 3 hypophysitis, grade 3 immune-mediated hepatitis, grade 2 acute kidney injury, grade 2 colitis, grade 2 enterocolitis, grade 2 immune-related hypothyroidism, grade 1 colitis, and grade 1 renal failure. No treatment-related deaths were reported.

The investigators concluded, “Cemiplimab exhibited clinically meaningful antitumor activity and an acceptable safety profile in patients with locally advanced basal cell carcinoma after HHI therapy.”

Alexander J. Stratigos, MD, of Andreas Syggros Hospital-National and Kapodistrian University of Athens, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Regeneron Pharmaceuticals and Sanofi. For full disclosures of the study authors, visit thelancet.com.