Clinical Pearls & Morning Reports

Posted by Carla Rothaus

Published October 26, 2022


How effective was cemiplimab in the trial by Gross et al.?

In a pilot study involving patients with cutaneous squamous-cell carcinoma, a high percentage of patients had a pathological complete response with the use of two doses of neoadjuvant cemiplimab before surgery. Gross et al. conducted a phase 2, confirmatory, multicenter, nonrandomized study to evaluate cemiplimab as neoadjuvant therapy in patients with resectable stage II, III, or IV (M0) cutaneous squamous-cell carcinoma. Read the NEJM Original Article here.

Clinical Pearls

Q: How are most patients with cutaneous squamous-cell carcinoma treated?

A: Most patients with cutaneous squamous-cell carcinoma present with early-stage disease that can be successfully treated with surgery alone. A small percentage of patients present with locoregionally advanced disease or disease with adverse histopathological features, which may be treated with adjuvant radiation therapy and possibly systemic therapy, in addition to surgery. Cutaneous squamous-cell carcinoma most commonly develops in sun-exposed areas, such as the head and neck, where surgery may lead to disfiguration. Thus, treatment can have a profound effect on psychosocial functioning and quality of life.

Q: What is cemiplimab?

A: Cemiplimab, an anti–programmed cell death 1 (PD-1) monoclonal antibody, has been approved for the treatment of metastatic or locally advanced cutaneous squamous-cell carcinoma for which no curative local treatment options are available. In studies involving patients with advanced cutaneous squamous-cell carcinoma, cemiplimab was associated with an objective response in 44 to 50% of patients, along with durable disease control and improved patient-reported quality of life. Other PD-1 inhibitors have also been shown to have activity in patients with advanced cutaneous squamous-cell carcinoma. A potential reason for the exceptional responsiveness of cutaneous squamous-cell carcinoma to immunotherapy is a high tumor mutational burden due to sun-related ultraviolet mutagenesis.

Morning Report Questions 

Q: How effective was cemiplimab in the trial by Gross et al.?

A: Neoadjuvant cemiplimab, administered at a dose of 350 mg every 3 weeks for up to four doses before surgery with curative intent, was associated with a pathological complete response in 51% of patients with stage II, III, or IV (M0) cutaneous squamous-cell carcinoma. Among the 17 patients (22%) who did not receive all four doses of neoadjuvant cemiplimab, the most common reason was disease progression, a finding that was based on either imaging (8 patients) or clinical evaluation (3 patients). Pathological responses were observed in both PD-L1–negative and PD-L1–positive patients, but the percentage of patients who had a pathological complete response was lower among patients with PD-L1 expression in less than 1% of tumor cells (20%; 95% CI, 4 to 48) than among those with PD-L1 expression in 1% of tumor cells or more (54%; 95% CI, 37 to 69).

Q: What were some of the limitations of the trial by Gross et al.?

A: Limitations to this study included the absence of a control group; without randomization, the possibility of selection bias cannot be ruled out. A high percentage of White male participants were enrolled. Furthermore, the relatively short median follow-up at the time of this report means that mature data regarding disease-free survival after surgery are not yet available.

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