Journal: NPJ breast cancer
This multicenter retrospective cohort study examined the incidence, timing, and predictors of immune-related toxicities in 700 breast cancer patients treated with immune checkpoint inhibitors across four NCI-designated centers (2014–2021). Most patients had triple-negative disease (77%); 61% had early-stage and 39% had metastatic breast cancer.
Immune-related toxicity—defined as events documented as ICI-related by the oncology provider or requiring steroids—occurred in 61% (430/700) of patients.
- Early toxicity only (≤90 days from ICI start): 37%
- Delayed toxicity only (>90 days from ICI start): 34%
- Both early and delayed events: 10%
Among patients with delayed toxicity:
- Developed while still on treatment: 60%
- Developed after treatment was completed: 23%
- Both on- and off-treatment events: 17%
Notably, 9.2% of those with delayed off-treatment toxicity developed it more than one year after ICI exposure.
Timing of delayed events:
- On-treatment delayed events: median onset 138 days (range 90–1380)
- Off-treatment delayed events: median onset 76 days (range 21–1144)
Risk factors and associations:
- Higher risk: greater ICI exposure, particularly beyond four cycles, and higher baseline eosinophil counts
- Lower risk of delayed events: metastatic disease status and the occurrence of early toxicity
The authors conclude that late and even very late immune-related toxicities are common in breast cancer patients treated with checkpoint inhibitors, underscoring the need for prolonged vigilance and clinician awareness well beyond the initial treatment period.