Background
The KEYNOTE-522 trial established neoadjuvant chemo-immunotherapy as the standard of care for triple-negative breast cancer (TNBC) (1). This audit evaluated real-world efficacy, safety, and permanent immune-related toxicities within a single-centre cohort.
Methods
This retrospective, single-centre audit included stage II/III TNBC patients receiving the neoadjuvant KEYNOTE-522 regimen between May 2023 and March 2026. Baseline characteristics, treatment modifications, pathological complete response (pCR), and adverse events (AEs) graded via the Common Terminology Criteria for Adverse Events (CTCAE) were analysed.
Results
Sixty-five female patients were evaluated; median age 53 years (range 43–66). Baseline ECOG performance status was 0–1 in 96.9% (n=63), 58.5% (n=38) were postmenopausal, and 15.4% (n=10) harboured a pathogenic germline mutation. Baseline staging included T1 (7.7%), T2 (66.2%), T3 (23.1%); 50.8% were node-positive. Median follow-up was 12.4 months, with an average of 9 treatment cycles completed.
All patients experienced treatment-related AEs, which were grade 3 or higher in 86.2% (n=56). Immune-related AEs (irAEs) occurred in 52.3% (n=34), most commonly endocrine toxicities or rash; 16.9% (n=11) were grade 3 or higher, and 18.4% (n=12) developed permanent endocrinopathies. Overall, 50.8% (n=33) discontinued treatment, while 38.5% (n=25) required dose reductions or delays. At surgery, 54% (n=27) achieved pCR and 64% (n=34) underwent breast-conserving surgery. Four patients experienced progressive disease.
Conclusion
Real-world efficacy of the KEYNOTE-522 regimen in achieving pCR aligns with clinical trial data (1,2). However, high rates of severe and permanent irAEs pose substantial long-term morbidity and economic burden on this young, otherwise healthy population. This underscores the need for ongoing studies evaluating treatment de-escalation strategies in patients who achieve a pCR.
References