Updated results from the phase 3 KEYNOTE-522 trial reveal that the addition of pembrolizumab to chemotherapy, both before and after surgery, significantly improves overall survival (OS) in patients with high-risk early-stage triple-negative breast cancer (TNBC). The findings, presented at the European Society for Medical Oncology (ESMO) Congress 2024, mark a significant advancement in the treatment of this aggressive form of breast cancer.
KEYNOTE-522 Trial Details
The KEYNOTE-522 trial is a randomized, double-blind study involving 1,174 patients with newly diagnosed stage II or III TNBC. Participants received neoadjuvant chemotherapy consisting of carboplatin-paclitaxel followed by doxorubicin or epirubicin plus cyclophosphamide. They were then randomized in a 2:1 ratio to receive either pembrolizumab or a placebo during the neoadjuvant phase, followed by adjuvant pembrolizumab or placebo after surgery.
The dual primary endpoints of the trial were pathological complete response (pCR) rate and event-free survival (EFS). Secondary endpoints included OS in all patients and in those with PD-L1–positive tumors.
Significant Improvement in Overall Survival
After a median follow-up of 75.1 months, the 5-year OS rate was 86.6% in the pembrolizumab arm compared to 81.7% in the placebo arm (HR, 0.66; 95% CI, 0.50-0.87; P = .00150). This translates to a 34% reduction in the risk of death with the addition of pembrolizumab to the treatment regimen. Lead study author Peter Schmid, MD, PhD, of Barts Cancer Institute at Queen Mary University in London, emphasized the clinical significance of these results, noting that the data demonstrate a meaningful improvement in survival for patients with early-stage TNBC.
Impact Across Subgroups
The survival benefit associated with pembrolizumab was observed across most prespecified subgroups, including those defined by PD-L1 expression, nodal status, tumor size, and tumor stage. Notably, patients experienced a benefit from pembrolizumab regardless of whether they achieved a pathological complete response (pCR).
For patients who achieved a pCR, the 5-year OS rate was 95.1% in the pembrolizumab arm and 94.4% in the placebo arm (HR, 0.69; 95% CI, 0.38-1.26). Among patients who did not achieve a pCR, the 5-year OS rate was 71.8% in the pembrolizumab arm and 65.7% in the placebo arm (HR, 0.76; 95% CI, 0.56-1.05), indicating that pembrolizumab provides a survival advantage even in cases where the tumor does not completely disappear.
Expert Commentary
Marleen Kok, MD, PhD, of the Netherlands Cancer Institute in Amsterdam, commented on the findings, stating that neoadjuvant pembrolizumab added to chemotherapy significantly improves overall survival in triple-negative breast cancer and should be considered the new standard of care for patients with stage II or III disease. She also highlighted the importance of identifying biomarkers to tailor treatment decisions and minimize over- and undertreatment.
Safety Profile
The safety profile of the pembrolizumab regimen remained consistent with previous analyses, with no new safety concerns identified. The most common immune-mediated side effects included hypothyroidism (15.1%), skin reactions (5.7%), and hyperthyroidism (5.2%).
Conclusion
The KEYNOTE-522 trial provides compelling evidence that the addition of pembrolizumab to neoadjuvant chemotherapy, followed by adjuvant pembrolizumab, significantly improves overall survival in patients with high-risk early-stage TNBC. These findings support the use of this regimen as a standard of care for this patient population, offering the potential for improved long-term outcomes.
