Dr LeVee on Immune-Related AEs Associated With ICIs in Early Breast Cancer

“We found a much higher rate of immune-related adverse [effects] than what has been previously published based on the [phase 3] KEYNOTE-522 trial.”

Alexis LeVee, MD, chief hematology/oncology fellow, City of Hope, discusses findings from a multi-institutional study investigating the rates of and risk factors for immune-related adverse effects (iRAEs) in patients with early-stage breast cancer treated with immune checkpoint inhibitors.

Findings were presented at the 2024 San Antonio Breast Cancer Symposium (SABCS). The multi-institutional study included 423 real-world patients who previously received immune checkpoint inhibitors for early-stage breast cancer, LeVee explains. The study included patients with stage I to III breast cancer who were treated with ICIs at 1 of 4 academic institutions between 2014 and 2024. An irAE was defined as a toxicity that was determined via an oncologist to be potentially or definitely related to immune checkpoint inhibitors or high dose steroids after the causative agent was not identified.

Of note, LeVee and colleagues found a higher rate of irAEs in their multi-institutional study compared with previous findings from the phase 3 KEYNOTE-522 trial (NCT03036488). The trial investigated the combination of pembrolizumab (Keytruda) and chemotherapy in previously untreated patients with stage II or III triple-negative breast cancer. Among patients from the multi-institutional study, 72.6% of patients experienced any-grade irAEs, LeVee says, and 18.9% experienced high-grade irAEs. She emphasizes that these findings were derived from patients treated in a real-world setting who were not selected for clinical trials because of comorbidities, which may be the reason for increased rates of irAEs.

LeVee notes that the association between comorbidities and increased rates of irAEs led them to focus on specific risk factors that may cause increased rates of irAEs. Based on their multivariate analysis, they found that patients older than age 50 and patients who had chronic kidney disease experienced higher rates of irAEs, she says. Therefore, it is crucial to identify patients at higher risk of irAEs to make informed treatment choices, she concludes.