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

BackgroundCutaneous 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 MethodsWe 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.ResultsThe 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.ConclusionsIn 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.

Immune checkpoint inhibitors in advanced cutaneous squamous cell carcinoma: A systemic review and meta‐analysis

“…The pooled analysis of eight studies 16–20,28–30 suggested that the overall incidence of all grade AEs was 76.9% (95% CI: 63.2%–90.7%). As for the AEs with ≥3 grades, the overall incidence was 20.2% (95% CI: 11.1%–29.3%) after meta‐analysis of eleven studies 16–22,28–31 . Further analysis indicated that pembrolizumab had better tolerability than cemiplimab.…”

“…Then, 1289 studies were excluded after initial screening of titles and abstracts. After reviewing the full text, 13 studies with 980 patients were finally included for final analysis 16–23,27–31 . Figure 1 showed the flowchart of the study screening process.…”

Identifying Candidates for Immunotherapy among Patients with Non-Melanoma Skin Cancer: A Review of the Potential Predictors of Response

“…Another real-world retrospective study involving 131 patients with advanced cSCC treated with cemiplimab identified a head and neck tumor location ( p -value = 0.007) and normal haemoglobin values ( p -value = 0.034) as positive predictors; on the other hand, location on the genitalia ( p -value = 0.041), treatment with any systemic antibiotic within 1 month of cemiplimab initiation ( p -value = 0.012), performance status ≥1 ( p -value = 0.012), chronic corticosteroids therapy ( p -value = 0.038), previous radiation therapy to lymph nodes ( p -value = 0.052), and previous chemotherapy ( p -value = 0.0020) were significantly associated with a worse response [ 45 ]. In a cohort of 30 elderly frail patients with la-cSCC ( n = 25) or m-cSCC ( n = 5) treated with cemiplimab, head/neck tumor location ( p -value = 0.016) and haemoglobin > 12 g/dL ( p -value = 0.042) were similarly associated with a higher RR [ 51 ].…”

“…Absolute lymphocyte count (ALC) was investigated as a predictor of response to ICIs in the aforementioned retrospective study by Hanna et al, and a higher median ALC at therapy initiation was correlated with a good response ( p -value < 0.01) [ 179 ]. Strippoli et al also identified the association between baseline low neuthophil/lymphocyte ratio and low platelet/lymphocyte ratio as a serological predictor of better response [ 51 ]. The underlying biological hypothesis is that lymphocyte count may serve as a surrogate for estimating the number of available circulating lymphocytes that could target the tumor, thus contributing to immunosurveillance [ 179 ].…”

Cemiplimab in advanced cutaneous squamous cell carcinoma: the UK experience from the Named Patient Scheme

“…Retrospective studies have evaluated cemiplimab in aCSCC. [5][6][7][8] The common feature of the real-world series is inclusion of immunocompromised patients and higher proportion of elderly patients. Both patient cohorts achieved comparable ORR and tolerability (low discontinuation rates) to patients treated in the clinical trial and add data on a group of patients who are underrepresented in clinical trials.…”