Effectiveness of neoadjuvent Cemiplimab for cSCC. Who gets it?

Gross ND, Miller DM, Khushalani NI, Divi V, Ruiz ES, Lipson EJ, Meier F, Su YB, Swiecicki PL, Atlas J, Geiger JL, Hauschild A, Choe JH, Hughes BGM, Schadendorf D, Patel VA, Homsi J, Taube JM, Lim AM, Ferrarotto R, Kaufman HL, Seebach F, Lowy I, Yoo SY, Mathias M, Fenech K, Han H, Fury MG, Rischin D. Neoadjuvant Cemiplimab for Stage II to IV Cutaneous Squamous-Cell Carcinoma. N Engl J Med. 2022 Sep 12. doi: 10.1056/NEJMoa2209813. Epub ahead of print. PMID: 36094839

A pathologic complete response was observed in 40 patients (51%; 95% CI: 39-62) and a pathologic major response was observed in 10 patients (13%; 95% CI: 6-22).

Clinical Pearls

• This phase 2, confirmatory study included 79 patients with resectable cutaneous squamous cell carcinoma who received neoadjuvant Cemiplimab.

• A pathologic complete response was observed in 40 patients (51%; 95% CI: 39-62) and a pathologic major response was observed in 10 patients (13%; 95% CI: 6-22). Adverse effects of any grade that occurred during the study period were reported by 69 patients (87%), of which 14 patients experienced grade 3 or higher adverse effects

• Use of the DecisionDx-SCC gene expression profile test may help identify patients in whom Cemiplimab may be most effective.

Discussion:

Cemiplimab, an anti-programmed cell death 1 (PD-1) monoclonal antibody, has been found to be effective in inducing a complete pathologic response (an absence of viable tumor cells in the surgical specimen) in 55% of patients in the past. The authors of this study hoped to provide confirmatory data and further determine the efficacy of Cemiplimab in this phase 2, confirmatory, multicenter, nonrandomized study.

Only patients 18 years of older with resectable stage II, III, or IV (M0) cutaneous squamous cell carcinoma for which primary surgery would be indicated in routine clinical practice were included in this study. The primary end point was a complete pathological response and the secondary end points included a major pathologic response (the presence of viable tumor cells that constitute up to 10% of the surgical specimen obtained after treatment). Following a screening period of up to 28 days, subjects received 350 mg of neoadjuvant Cemiplimab intravenously every 3 weeks for up to a total of 12 weeks.

79 patients initially received the study treatment. Of those, 40 (51%; 95% CI: 39-62) exhibited a pathologic complete response and 10 (13%; 95% CI, 6 to 22) exhibited a pathologic major response to Cemiplimab. 69 patients (87%) exhibited adverse effects of any grade, regardless if attributable to the treatment, during the study. The most common adverse effects included fatigue (24 patients; 30%), diarrhea, nausea, and maculopapular rash (11 patients each, 14%). Four adverse events that were fatal occurred during the study, one of which was considered to possibly be related to Cemiplimab treatment.

While this study sheds light on the effectiveness of Cemiplimab, one clinical dilemma which may subsequently arise is deciding which patients will benefit most from it. A recent study by Wysong et al. found the use of a 40-gene expression profile test (DecisionDx-SCC 40 GEP) can stratify patients with high-risk cSCC. The adoption of this GEP in the setting of patients with high-risk cSCC may better predict in which patients Cemiplimab will provide the greatest balance of efficacy and tolerability.