Pembrolizumab Brings Heavy Toxicity Burden for Older Breast Cancer Patients in Real-World Care

Older adults with triple-negative breast cancer who received pembrolizumab-based therapy in routine oncology practice experienced high rates of serious toxicity, according to a cohort study published in Breast Cancer Research and Treatment. The research, led by Claire E. Smith and Rachel A. Freedman and collaborators, reviewed medical records of 136 patients aged 65 and older treated between 2021 and 2024, examining how this immunotherapy combination performs in everyday clinical care. The cohort included 85 patients with early-stage disease and 51 with metastatic disease, with a median age of 71 and a range extending to 91 years.

Among those with early-stage disease, 42 percent received the neoadjuvant KEYNOTE-522 regimen. The investigators examined immune-related adverse events, hospitalizations, the percentage of the ideal dose actually delivered, treatment discontinuation, and factors associated with pathologic complete response. Among patients with metastatic disease, progression-free and overall survival were analyzed using Kaplan-Meier methods.

The toxicity findings were substantial. Among patients with early-stage disease, 41 percent required hospitalization, 39 percent experienced immune-related adverse events, and 4 percent died of treatment-related causes. Patients older than 70 had more immune-related adverse events and received a lower percentage of the ideal dose than their younger counterparts, with the mean ideal dose across the early-stage group standing at 82 percent.

For patients with metastatic disease, the safety picture was similar. Forty-three percent were hospitalized, 18 percent required admission to the intensive care unit, and 41 percent experienced immune-related adverse events. The authors conclude that in this cohort they observed high rates of serious toxicity.

Effectiveness results also fell short of expectations. In the early-stage group, 43 percent achieved a pathologic complete response, a rate the authors describe as lower than expected. Notably, no clinical or treatment variables were associated with achieving a pathologic complete response, meaning the researchers could not identify which older patients were most likely to benefit from the intensive regimen.

Outcomes in metastatic disease were measured with survival analysis. With a median follow-up of 29 months, median progression-free survival was 5.45 months, with a 95 percent confidence interval of 3.8 to 7.8 months, and median overall survival was 23.1 months, with a 95 percent confidence interval of 18.6 to 35.4 months. The authors characterize overall survival in this group as short.

The study's design carries important limitations. As a medical record review rather than a randomized trial, it cannot establish causal relationships between treatment modifications and outcomes, and the cohort size of 136 patients limits the statistical power to detect associations. The findings describe the experience of the centers involved and may not generalize to all practice settings.

The authors conclude that in this cohort of older adults with triple-negative breast cancer receiving pembrolizumab-containing treatment, they observed high rates of serious toxicity, lower-than-expected pathologic complete response rates in early-stage disease, and short overall survival in metastatic disease. The results add real-world evidence on treatment patterns, efficacy, and safety for a population in whom data have been limited, and they may inform future studies that deliberately include older adults with this diagnosis.

Subject of Research: Real-world efficacy and toxicity of pembrolizumab-containing therapy in older adults with triple-negative breast cancer

Article Title: Efficacy and toxicity for pembrolizumab-containing therapy in older adults with triple-negative breast cancer: insights from routine oncology practice

Article References: Smith, C. E., Rami, A., Li, T., Tayob, N., Patel, P., Burstein, H. J., McAllister, S., Abelman, R., & Freedman, R. A. (2026). Efficacy and toxicity for pembrolizumab-containing therapy in older adults with triple-negative breast cancer: insights from routine oncology practice. Breast Cancer Research and Treatment, 220(1), Article 16. https://doi.org/10.1007/s10549-026-08112-2

Image Credits: AI Generated

DOI: 10.1007/s10549-026-08112-2

Keywords: triple-negative breast cancer, pembrolizumab, immunotherapy, older adults, immune-related adverse events, hospitalization, pathologic complete response, progression-free survival, overall survival, KEYNOTE-522, geriatric oncology, real-world evidence