Dupilumab for the treatment of dermatologic adverse events associated with MEK and EGFR inhibitors.

3143 Background: Mitogen activated protein kinase kinase inhibitors (MEKi) and epidermal growth factor receptor inhibitors (EGFRi) are targeted therapies used in the treatment of various cancers. Dermatologic adverse events (dAEs) are common with these medications. Dupilumab, a human monoclonal antibody that targets IL-4, is an FDA approved therapy for the treatment of atopic dermatitis. It has also shown utility in the treatment of many other skin disorders, including toxicities associated with anticancer therapies. In our study, we aim to evaluate the efficacy and safety of dupilumab for the treatment of MEKi/EGFRi associated dAEs. Methods: Patients who received dupilumab for the treatment of a dAE attributed to MEKi or EGFRi from 3/1/2017 to 10/1/2022 were identified at Memorial Sloan Kettering Cancer Center. Severity of dAEs was graded at baseline and follow up using Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Patient response to dupilumab was categorized into complete response (CR) (reduction to grade 0), partial response (PR) (reduction to grade 1), or no response (NR) (including change from grade 3/2 to grade ≥ 2). Results: A total of 17 patients (median age 62 years [5 – 87], 58.8% female) who received dupilumab for MEKi (70.6%) or EGFRi (29.4%) related dAEs were identified. Two patients on MEKi were also on concomitant BRAF inhibitors. Patients were white (88.2%), black (5.9%), and Asian (5.9%) and were all undergoing treatment for solid tumors. All dAEs had an eczematous phenotype; 16 were grade 2 (88.2%) and one (5.9%) was grade 3. The median time from dAE development to initiation of dupilumab was 121 days (5 – 1330). Following treatment, 15 patients (88.2%) experienced improvement, with 46.7% and 53.3% achieving CR and PR, respectively. Patients were on dupilumab for a median of 89 days (0-2556), with CR and PR patients exhibiting initial documented response after a median of 30 days (6 – 173). The median CTCAE grade decreased from 2 to 1, and the number of patients on topical and systemic steroids following addition of dupilumab decreased from 17 (100%) to 7 (41.2%) and 5 (29.4%) to 1 (5.9%), respectively. As a result of intolerable anti-cancer therapy-associated dAEs, 4 patients (all on MEKi) initially discontinued their antineoplastics. Three patients (75%) were successfully rechallenged with their original MEKi, while 1 (25%) was switched to another MEKi without subsequent dAE recurrence. No patients reported adverse events to dupilumab treatment. Conclusions: Patients may experience eczematous eruptions while undergoing treatment with MEKi or EGFRi. Dupilumab may be a safe and effective steroid sparing therapeutic option for the management of these dAEs.