Cemiplimab in an Elderly Frail Population of Patients With Locally Advanced or Metastatic Cutaneous Squamous Cell Carcinoma: A Single-Center Real-Life Experience From Italy

Abstract

Background: Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer whose incidence is growing parallel to the lengthening of the average lifespan. Cemiplimab, an antiPD-1 monoclonal antibody, is the first approved immunotherapy for patients with locally advanced CSCC (laCSCC) or metastatic CSCC (mCSCC) thanks to phase I and II studies showing high antitumor activity and good tolerability. Nevertheless, at present, very few data are available regarding cemiplimab in real-life experience and in frail, elderly, and immunosuppressed patients as well as regarding biomarkers able to predict response so as to guide therapeutic choices.

Patients and methods: We built a retroprospective cohort study including 30 non-selected patients with laCSCC (25) and mCSCC (five) treated with cemiplimab from August 2019 to November 2020. Clinical outcomes, toxicity profile, and correlations with disease, patients, and peripheral blood parameters are explored.

Results: The median age was 81 years (range, 36-95), with 24 males and five patients having an immunosuppressive condition, while the frailty prevalence was 83% based on index derived from age, Eastern Cooperative Oncology Group performance status, and Charlson Comorbidity Index. We reported 23 responses (76.7%) with nine complete responses (30%). A statistically significant higher response rate was observed in head and neck primary tumors and in patients with hemoglobin level >12 g/dl. No difference was observed with respect to frailty, median age, sex, and body mass index. The baseline low neuthophil/lymphocyte ratio and low platelet/lymphocyte ratio resulted to be also correlated with a better response. Moreover, lymphocyte, neutrophil, and monocyte behaviors had an opposite trend in responders and non-responders. An overall response was reported in four of five immunosuppressed patients. Seventeen patients (57.6%) have an ongoing response and are still alive. Six responders had interrupted treatment (two for toxicity and four for personal choice) but maintained their response. The treatment was well tolerated by the majority of patients. The most common adverse events were fatigue in seven patients (23.3%) and skin toxicity in 10 patients (33.3%), including pruritus in six patients, rash in three patients, and bullous erythema in one patient.

Conclusions: In our real-life experience, cemiplimab showed a high antitumor activity with acceptable safety profile similar to those in trials with selected patients. Moreover, its antitumor activity resulted to be not impaired in very elderly patients and in those with immunocompromised status.

Keywords: advanced cutaneous squamous cell carcinoma; cemiplimab; checkpoint inhibitors; elderly patients; immunocompromised patients.

Figure 1

Representative cases of patients obtaining a major response to cemiplimab. (A) An 88-year-old female with a large locally advanced cutaneous squamous cell carcinoma (laCSCC) of the left nasal-infraorbital region achieving a complete response. Neither had she received prior radiotherapy nor anticancer systemic therapy. (B) An 89-year-old man with a large laCSCC tumor of the right parotid region obtaining a complete response after 6 cycles of cemiplimab and concurrent radiotherapy. (C, D) A 67-year-old man with metastatic cutaneous squamous cell carcinoma in immunosuppressive therapy due to a previous kidney transplantation. The patient achieved a near-complete response both at the right zygomatic area and the metastatic lung lesions.

Figure 2

(A) Swimming plot showing the time and duration of response (30 patients). Each horizontal line represents one patient. (B) Waterfall plot representing the rate of change in target cutaneous squamous cell carcinoma lesions from baseline during the cemiplimab course.

Figure 3

Forest plot of response in selected subgroups of patients according to the main clinical and hematological characteristics. For hematologic parameters, we considered pre-therapy values: only 24 patients were considered eligible (three patients were excluded for concomitant hematological tumors, one for thalassemia major, and two patients for concomitant immunosuppressive therapy).

Figure 4

Kaplan–Meier curves for progression-free survival (A) and overall survival (B).

Figure 5

Hemoglobin values according to clinical response.

Figure 6

Trends of the main blood parameters according to clinical response. Twenty-four patients were considered eligible (three patients were excluded for concomitant hematological tumors, one for thalassemia major, and two for concomitant immunosuppressive therapy). For non-responders, data from the 6-month sampling are not available.