1. After neoadjuvant treatment with celmiplimab, half of the patients were found to have a complete pathological response

2. Almost a fifth of patients experienced grade 3 or higher adverse events. Common adverse events included fatigue, rash, nausea, diarrhea, and immune-related events.

Evidence Rating Level: 2 (Good)

Study Rundown: Celmiplimab is a programmed cell death 1 (PD-1) monoclonal antibody that has been investigated as a curative treatment option for cutaneous squamous cell carcinoma. High functioning patients with resectable stage II, III, or IV carcinoma were recruited from three countries. There was only one arm. Surgical specimens from resection were then analyzed by an independent review for complete or major pathological response meaning the absence of viable tumor cells and up to ten percent of viable tumor cells respectfully. Complete and major pathological response was observed in more than half of the patients, with a quarter of patient samples showing no response (more than ten percent viable cells seen). Common adverse events included fatigue, rash, nausea, diarrhea, and immune-related events. Almost a fifth of patients had grade 3 or higher adverse events. There was no clear association between biomarker or mutational burden with pathological outcomes. Limitations to this study included the small sample size, lack of a control group, and short follow-up time. The strengths of this study included a thorough independent review of pathological specimens. Overall, neoadjuvant celmiplimab had an associated pathological response in resectable cutaneous carcinoma and has a potential for inclusion in future treatment modalities.

Click to read the study in NJEM

Relevant Reading: PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma

In-Depth [prospective cohort]: This prospective phase II study included 79 patients, with a majority (85%) of patients being male, and 91% having carcinoma of the head and neck. Neoadjuvant treatment consisted of cemiplimab 350mg every 3 weeks, up to four doses, with 78% of participants that received all four doses. Complete pathological response occurred in 51% of patients (95% CI, 39 to 62) along with 13% (95% CI, 6 to 22) of patients showing a major pathological response. 25% of patients had no pathological response. The most common adverse events included fatigue (30%), diarrhea (14%), nausea (14%), rash (14%), and immune-related events (15%). Grade 3, 4, and 5 adverse events occurred in 10%, 3%, and 5% respectively. Biomarker PD-L1 was assessed, and this study found a greater association, although no statistical significance, with pathological response in PD-L1 positive (54%, 95%CI, 37 to 69) compared to PD-L1 negative (20%, 95% CI, 4 to 48). Similarly, it was found that patients with a high mutational burden were associated with a higher pathological response of (56%, 95% CI, 35 to 76) compared to those with a lower mutational burden (20%, 95% CI, 7 to 41), although this finding had no statistical significance. Overall, patients with stage II-IV carcinoma showed promising pathological responses to neoadjuvant cemiplimab and further trials may lead to its use in clinical practice.

Image: PD

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