Cutaneous adverse effects of combination epidermal growth factor receptor inhibitor and immune checkpoint inhibitor...

Epidermal growth factor receptor inhibitors (EGFRIs) and immune checkpoint inhibitors (ICIs) show promising efficacy in colorectal cancer and head and neck squamous cell carcinoma therapy, especially in combination. However, given the many cutaneous adverse effects (CAE) associated with each, there is concern for overlap and exacerbation of toxicities. EGFRIs are associated with acneiform rashes and paronychia, while ICIs are associated with lichenoid dermatitis and psoriasis. Xerosis, pruritus, and eczema are seen with both drugs. Understanding the CAEs of EGFRI-ICI combination therapy may guide the management of toxicities and improve adherence to life-saving therapy.

A retrospective chart review of patients treated with EGFRI/ICI combination between January 1, 2015, and May 21, 2024, was performed. Data on demographics, cancer type, and CAE incidence, duration, and management were manually investigated.

Forty-four patients were identified on EGFRI/ICI therapy, with 26 patients (59%) developing a total of 42 CAEs. Patients received cetuximab-pembrolizumab (72%) or cetuximab-nivolumab (28%) therapy. The most common CAEs seen were acneiform eruption (33%) and eczema (18%). Most CAEs were caused by EGFRI (62%) with 12% attributable to ICI, and 24% of CAEs attributed to either/both drugs. Most CAEs were reported as mild to moderate.

Combination EGFRI/ICI therapy is quickly becoming standard treatment in certain cancers, and the incidence of CAEs is high (59%) in this population. CAEs appear to be skewed towards EGFRI rashes and low-grade severity. A prospective trial is warranted to further understand the impact of CAEs for patients being treated with this combination therapy.