Understanding Second Primary Tumors (SPTs) in Cutaneous Squamous Cell Carcinoma (CSCC) Patients Treated with Cemiplimab
A study investigated the incidence of second primary tumors (SPTs) in patients with high-risk cutaneous squamous cell carcinoma (CSCC) treated with adjuvant cemiplimab, compared to a placebo control group. A total of 191 SPTs were reported across both arms of the study: 68 in the cemiplimab arm and 123 in the placebo arm.
Analysis focused on annualized, adjusted rates of SPTs, revealing a significant difference during the active treatment period. The rate of SPTs in the cemiplimab arm during treatment was 1.2, while the placebo arm experienced a rate of 2.8. Interestingly, the number of patients experiencing one or more SPTs was comparable between the two groups. The disparity in overall SPT numbers stemmed from a small subset of patients who developed a disproportionately high number of tumors. Specifically, during the treatment period, no patients on cemiplimab experienced six or more SPTs, whereas three placebo patients had seven, nine, and 34 SPTs respectively.This pattern continued, though to a lesser extent, during the follow-up period, with one cemiplimab patient and three placebo patients falling into the six-or-more SPT category.
While SPT rates appeared higher during the active treatment phase,researchers acknowledged uncertainty about whether this difference would persist with longer follow-up.The data from the treatment period, characterized by close patient monitoring at regular intervals, demonstrated the clearest distinction between the two arms. Rates in the follow-up period showed less divergence, suggesting a potential waning of cemiplimab’s preventative effect over time.
investigation into patient or disease-related factors predisposing to SPTs is ongoing, but it is recognized that patients with extensive field cancerization – characterized by multiple actinic keratoses and a history of non-melanoma skin cancers - are considered a high-risk group.
Despite the observed SPT incidence, the study suggests that surveillance recommendations for patients treated with cemiplimab, whether in advanced or adjuvant settings, should remain consistent with standard dermatological practice. patients often report skin improvement with cemiplimab, but remain susceptible to developing second primary tumors.
From a benefit-risk perspective, the SPT data is considered an interesting observation requiring further study, but should not currently influence clinical decision-making regarding adjuvant cemiplimab. Given its FDA approval and pending EU recommendation, cemiplimab should be considered a standard-of-care option for patients with high-risk CSCC based on pathologic and clinicopathologic features indicating a need for adjuvant treatment.
