SITC 2024: Adding IL-4 Inhibitor to PD-1 Inhibitor Therapy for ER-Positive Breast Cancer

By: Julia Cipriano, MS
Posted: Tuesday, November 19, 2024

Angel Arnaout, MD, MBA, of the Provincial Health Services Authority, Vancouver, and colleagues conducted a phase II window-of-opportunity trial to determine whether the addition of the interleukin (IL)-4 receptor antagonist dupilumab to PD-1 inhibitor therapy with cemiplimab-rwlc may enhance responses within estrogen receptor (ER)-positive breast cancer tumors. Presented during the 2024 Society for Immunotherapy of Cancer (SITC) Annual Meeting (Abstract 716), their findings seem to support further investigation of this therapeutic strategy in larger neoadjuvant trials aimed at improving immunotherapy in such immunologically “cold” tumors.

A total of 20 newly diagnosed patients with primary invasive T1 or T2 ER-positive, HER2-negative breast cancer were randomly assigned in a 1:1 ratio to receive a single dose of 350 mg of intravenous cemiplimab alone (n = 10) or in combination with 600 mg of subcutaneous dupilumab (n = 10) in the preoperative setting. Baseline and after-treatment (ie, 1 week before surgical resection) biopsy samples were collected and profiled. The mean patient age was 61.5 years, and the average tumor size was 2.5 cm.

Most adverse events were documented as grade 1 toxicities; fatigue was reported most and with the same frequency in both treatment arms. In 40 pretreatment biopsies, the most frequently mutated genes included PIK3CA (25%), CDH1 (25%), TP53 (23%), and KMT2C (20%). The investigators identified frequent copy number changes in CCND1 (20%), FGF19 (20%), and FGF4 (20%). Differential gene expression and subsequent pathway analysis of enriched genes demonstrated enhanced interferon signaling, antigen presentation, and processing pathways with cemiplimab plus dupilumab; proteomic profiling showed minimal changes in immune cell composition, according to the investigators.

Disclosure: No information regarding conflicts of interest was provided.

2024 SITC Annual Meeting

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