Adjuvant cemiplimab therapy significantly reduced recurrence among patients with resected cutaneous squamous-cell carcinoma (cSCC) with disease-free survival of 87% vs 64% with placebo at 24 months, according to a phase 3 randomized controlled trial of 415 patients.
The immunotherapy provided substantial benefits for both locoregional and distant recurrence. Locoregional recurrence occurred in 9 patients treated with cemiplimab compared with 40 patients receiving placebo. Distant recurrence occurred in 10 vs 26 patients respectively. Two-year freedom from locoregional recurrence was 95% with cemiplimab and 77% with placebo. Two-year freedom from distant recurrence was 94% and 84%.
Grade 3 or higher adverse events occurred in 24% of patients treated with cemiplimab vs 14% with placebo. Immune-related adverse events were more common with cemiplimab (23% vs 6%). One treatment-related death from myositis occurred in the cemiplimab group.
Overall survival data were not yet mature. At 2 years, survival was 95% with cemiplimab and 92% with placebo. With longer follow-up, 33 deaths occurred, including 15 in the cemiplimab group and 18 in the placebo group. Many patients who received placebo crossed over to cemiplimab after recurrence, and 43% of these patients achieved an objective radiographic response.
The trial enrolled patients across 107 sites in 16 countries who had undergone curative-intent resection and postoperative radiotherapy within 2 to 10 weeks before randomization for tumors with high-risk features including extracapsular extension, three or more involved nodes, T4 tumors with bone invasion, perineural invasion of major nerves, in-transit metastases, or locally recurrent tumors with adverse features.
Treatment consisted of cemiplimab 350 mg intravenously every 3 weeks for 12 weeks, followed by 700 mg every 6 weeks for up to 36 weeks. Median follow-up was 24 months.
“Most recurrences were observed in the first year after surgical resection and the completion of adjuvant radiotherapy — findings that are consistent with the natural history of cutaneous squamous-cell carcinoma to recur rapidly,” wrote Danny Rischin, MD, Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia, and colleagues. Patient-reported outcomes showed no clinically meaningful differences in global health status or quality of life between groups during treatment.
Study limitations include immature overall survival data and potential influence from placebo patients who crossed over to cemiplimab after recurrence. The trial was conducted across multiple international sites with median follow-up of 24 months. Longer follow-up is needed to assess durability of benefit and long-term safety.
The researchers concluded that adjuvant cemiplimab following surgery and radiotherapy delayed recurrence in patients with high-risk cSCC. Monitoring is ongoing to determine its effect on overall survival.
Full disclosures can be found in the study.
Source: New England Journal of Medicine