Benralizumab relieves Eosinophil-Related Cutaneous Adverse Events from Cancer Therapy: A Nonrandomized Phase 2 Trial.

Abstract

Eosinophil-related cutaneous adverse events (ercAEs) are common following systemic cancer therapies and often impact health-related quality of life (HRQoL). Here we investigate the efficacy and safety of benralizumab for ercAEs following systemic cancer therapies. This single-arm, single-center, open-label, phase 2 trial (NCT04552288) in patients with cancer and systemic therapy-associated ercAEs, was performed from September 2020 to October 2023. Benralizumab 30 mg was administered subcutaneously in the approved dosing of q4w (x3), followed by q8w (x3). The primary endpoint was clinical response (reduction in ercAEs to CTCAE grade ≤1 by Week 4). Secondary endpoints included, HRQoL, rash body surface area (rash-BSA), eosinophil levels, and AEs. At baseline (N = 47), ercAEs were related to PI3K inhibitors in 47%, checkpoint inhibitors in 21%, tyrosine kinase inhibitors in 9%, and antibody-drug conjugates in 9%; ercAEs were grade 2 and 3 in 49% and 51% of patients, respectively. Of the 42 patients evaluable for the primary endpoint, 76% patients (n = 32/42) responded to treatment by Week 4; median ercAE grade decreased from 2 to 1 (P < .0001). Patients exhibited improved HRQoL, reduced mean rash-BSA, and decreased peripheral eosinophils. All patients with ercAEs following alpelisib (n = 18) or enfortumab vedotin (n = 4) responded by Week 4 (both P < .05). Most AEs were mild to moderate and likely unrelated to benralizumab. Benralizumab demonstrated favorable efficacy and safety against grade 2/3 ercAEs following systemic cancer therapies. Further investigation in larger placebo-controlled trials is warranted.