Journal of Clinical and Aesthetic Dermatology • Hot Topics in Squamous Cell Carcinoma July 2024 • Research Summary

RESEARCH SUMMARY—Real-world Experience of Immune Checkpoint Inhibitors in Older Patients with Advanced Cutaneous Squamous Cell Carcinoma

The incidence of cutaneous squamous cell carcinoma (cSCC) is increased in older individuals due to cumulative exposure to ultraviolet radiation. For patients with advanced cSCC who cannot undergo surgery or radiotherapy, immune checkpoint inhibitors (ICIs) are the current standard of care. ICIs tend to be more tolerable than chemotherapy, particularly among older individuals. However, older individuals have been underrepresented in clinical trials, and ICI therapy can cause immune-related adverse events (irAEs), with poorer outcomes reported in patients with greater comorbidity burden. In this single-center, retrospective study, McLean et al1 assessed the safety and efficacy of ICI therapy in patients with advanced cSCC aged 70 years or older, including patients with comorbidities, immunocompromised status, and poor Eastern Cooperative Oncology Group performance status (ECOG PS). Their findings are summarized below

Patients with locally advanced/metastatic cSCC treated with cemiplimab 350mg three times per week through an access scheme or pembrolizumab prior to availability of the access scheme were eligible for inclusion. Patients were ineligible to participate in clinical trials at ICI commencement. Patients with a poor ECOG PS were eligible if their treating physician deemed them fit to receive ICI therapy.

Among 53 patients, median age was 81.8 years. Eighty-one percent of patients (n=43) were male. Most patients had an ECOG PS of 0 (36%); 30, 26, and eight percent of patients had an ECOG PS of 1, 2, and 3, respectively. In 89 percent of patients (n=47), primary cSCC lesion was located at the head and neck. Distant metastasis was present in 74 percent of patients (n=39) at ICI initiation. Only two patients were treated with pembrolizumab. Seventy percent of patients (n=37) had undergone previous surgery for primary disease, while 47 percent (n=25) had received prior radiotherapy.

Median Charlson Comorbidity Index (CCI) score was 9. Cardiac comorbidities were the most common, present in 25 patients (47%), followed by diabetes mellitus (n=17, 32%), chronic kidney disease (n=13, 25%), and hematological malignancy (n=13, 25%). Eighteen patients (34%) were immunocompromised, including the 13 patients with hematological malignancy. Six patients (11.3%) had an autoimmune disease.

Seven patients were not evaluable for efficacy analyses. The overall response rate (ORR) was 57 percent. Complete response was achieved by 33 percent of patients (n=15), while 24 percent (n=11) experienced partial response. Twenty-six percent of patients (n=12) had stable disease. Progressive disease as best response was only reported in 17 percent of patients (n=8). Among immunocompromised patients, 40 percent (n=6) experienced stable disease as their best response, and only 13 percent (n=2) had progressive disease. Complete and partial responses were reported in 27 (n=4) and 20 percent (n=3) of immunocompromised patients, respectively. The ORR of immunocompromised patients was 47 percent, compared to 61 percent for nonimmunocompromised patients.

There was a median follow-up of 9.1 months. Twelve-month progression-free survival (PFS) was 41 percent, and 12-month overall survival (OS) was 63 percent. Poorer ECOG PS was associated with decreased PFS and OS, according to Cox regression analysis. Other variables, including older age, sex, immunocompromised status, and CCI score, were not associated with survival. Seventeen patients had died at follow-up, but only six deaths were attributable to cSCC.

Seventeen patients (32%) experienced at least one any-grade irAE. Six patients (11%) discontinued treatment due to irAEs, and no treatment-related deaths occurred. Thirteen patients (24.5%) developed a Grade 2 or higher irAE. One patient had Grade 3 skin toxicity, and one patient experienced Grade 3 myocarditis and colitis. Rheumatological irAEs were the most frequent, reported in seven patients (grade 1: n=1, grade 2: n=6); polymyalgia rheumatica occurred in three patients, inflammatory arthropathy in two patients, myositis in one patient, and vasculitis flare in one patient. Six patients developed skin irAEs (Grade 1: n=2, Grade 2: n=3, Grade 3: n=1). Three cases of thyroiditis were reported. All six patients with a pre-existing autoimmune disease experienced an irAE; of these patients, three had a flare of their existing autoimmune disease. There was a significant association between presence of autoimmune disease and Grade 2 or higher irAEs, though this finding is limited due to the small sample size. Immunocompromised status was not associated with Grade 2 or higher irAEs.

This study had several limitations, including the small sample size and retrospective design. Imaging techniques for tumor assessments varied, and imaging and disease assessments were not centrally reviewed. Additionally, PFS estimates lacked optimal precision because imaging assessments intervals were implemented according to standard of care.

The authors concluded that among patients aged 70 years or older with advanced or metastatic cSCC, ICI treatment is effective with a tolerable safety profile, including those with comorbidities and immunocompromised status.