KEYNOTE-522: adding pembrolizumab before and after surgery in early triple-negative breast cancer
Adding the immunotherapy pembrolizumab to chemotherapy before surgery, then continuing it afterwards, cut the risk of relapse or death by about a third in stage II-III triple-negative breast cancer and later improved survival.
Phase 3, double-blind trial randomising 1,174 patients with untreated stage II-III triple-negative breast cancer (2:1) to neoadjuvant pembrolizumab or placebo plus carboplatin-paclitaxel then anthracycline-cyclophosphamide, followed by surgery and nine cycles of adjuvant pembrolizumab or placebo. Dual primary endpoints were pathological complete response (pCR) and event-free survival (EFS).
The 2020 report showed pCR 64.8% vs 51.2%. This 2022 report showed the EFS benefit: 36-month EFS 84.5% vs 76.8% (HR 0.63). A 2024 report added an overall survival benefit (5-year OS 86.6% vs 81.7%, HR 0.66). It established chemo-immunotherapy as the standard for stage II-III TNBC regardless of PD-L1 status.
- pCR (ypT0/Tis ypN0) 64.8% with pembrolizumab vs 51.2% with placebo, a 13.6-point absolute gain (2020 interim report).
- 36-month event-free survival 84.5% vs 76.8%; HR for event or death 0.63 (95% CI 0.48-0.82).
- Benefit was seen regardless of PD-L1 expression (CPS), unlike in the metastatic setting.
- Patients with residual disease still did worse than those with pCR, but pembrolizumab improved EFS in both groups.
- 5-year overall survival 86.6% vs 81.7%, HR 0.66 (2024 update).
For stage II-III triple-negative breast cancer, chemotherapy plus pembrolizumab before surgery and pembrolizumab alone afterwards is now the standard approach worldwide, and the survival gain is real, not just a surrogate. It does not apply to stage I disease or to hormone-receptor-positive or HER2-positive cancers. The price is a year of immunotherapy with a meaningful chance of a permanent endocrine side effect such as hypothyroidism or adrenal insufficiency.
- The trial cannot say whether the adjuvant phase of pembrolizumab is needed for patients who reach pCR; de-escalation trials are testing this.
- Immune-related adverse events (thyroid, adrenal, pituitary) are often permanent.
- Carboplatin was part of the backbone in both arms, so the trial does not isolate the contribution of platinum.
- The control arm did not include capecitabine for residual disease, which some regard as a weaker comparator.