Pembrolizumab, a core asset of Merck, is a programmed death receptor-1 (PD-1) immune checkpoint inhibitor approved across multiple tumor types, including triple-negative breast cancer (TNBC). In May 2020, the US FDA approved pembrolizumab in combination with chemotherapy for high-risk early-stage TNBC based on the Phase III KEYNOTE-522 study. In this trial, neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab demonstrated statistically significant and clinically meaningful improvements in pathological complete response (pCR) and event-free survival (EFS) compared with chemotherapy alone. With longer-term follow-up, the regimen has also demonstrated a sustained overall survival (OS) benefit, establishing it as a curative-intent standard of care in early-stage TNBC. Absolute benefit of pembrolizumab remains stable over around 8 years, cementing the perioperative regimen's curative potential in high-risk early TNBC.

 

KOL insights

“KEYNOTE-522 was the neoadjuvant/adjuvant study that investigated and led to [the FDA approval of] 1 year of pembrolizumab for patients with early stage II to III disease starting in the neoadjuvant setting along with chemotherapy, followed by surgery and continuation of pembrolizumab [as adjuvant therapy].” –Expert Opinion

“The addition of pembrolizumab does not significantly exacerbate traditional chemotherapy side effects. We have to differentiate here the chemotherapy related adverse events which are very well known and have to deal with neutropenia, gastrointestinal adverse events basically nausea and vomiting.”–Expert Opinion

Conclusion

Breast cancer is the most common cancer in women in the United States, accounting for ~306,800 cases in 2025. TNBC accounts for approximately 15% of all breast cancer cases.

In the current competitive landscape, the focus is shifting toward next-generation antibody–drug conjugates (ADCs) and IO–ADC combinations rather than competing checkpoint inhibitors. Emerging agents such as datopotamab deruxtecan (Daiichi Sankyo/AstraZeneca) are advancing in TNBC development, reflecting a broader evolution toward ADC-based backbone strategies and chemotherapy-reduced combination approaches in earlier treatment settings. However, these ADC-based regimens remain investigational in the curative early-stage setting and have not demonstrated long-term survival outcomes comparable to KEYNOTE-522. Consequently, pembrolizumab plus chemotherapy continues to define the benchmark in high-risk early TNBC and serves as the reference standard against which all emerging IO–ADC combination strategies are being evaluated.