Clinical Summary: 

• Design/Population: Final analysis of the phase 3 KEYNOTE-522 trial evaluating neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab versus chemotherapy alone in patients with stage 2/3 triple-negative breast cancer.
• Key Outcomes: After nearly 8 years of follow-up, pembrolizumab continued to demonstrate durable improvements in event-free survival and overall survival, with benefits maintained across all major clinical subgroups. Improved outcomes were observed in both patients achieving pathologic complete response and those with residual disease after neoadjuvant therapy.
• Clinical Relevance: These long-term findings confirm pembrolizumab plus chemotherapy as the standard of care for early-stage triple-negative breast cancer and demonstrate sustained survival benefits extending well beyond treatment completion.

Peter Schmid, MD, PhD, Barts Cancer Institute, London, United Kingdom, discusses final long-term analysis results from the phase 3 KEYNOTE-522 trial evaluating pembrolizumab in combination with chemotherapy for patients with stage 2/3 triple-negative breast cancer. The study previously established improvements in pathologic complete response, event-free survival, and overall survival, leading to widespread adoption of pembrolizumab-based therapy in the curative setting.

With nearly 8 years of follow-up, the trial continues to demonstrate durable survival benefits and sustained separation of event-free and overall survival curves. The analysis also suggests that pembrolizumab favorably alters tumor biology, as improved outcomes were observed even among patients with residual disease following neoadjuvant treatment, further reinforcing the long-term value of immunotherapy in early-stage triple-negative breast cancer.

Dr Schmid presented these results at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

Transcript: 

I'm Peter Schmid, I'm a medical oncologist and work at Barts Hospital in London. At ASCO 2026, we saw the final data from the KEYNOTE-522 trial. 

KEYNOTE-522 has really been a pivotal study in the management of patients with early-stage triple-negative breast cancer. It firmly established pembrolizumab in combination with chemotherapy as preoperative therapy, followed by pembrolizumab in the adjuvant setting for another 6 months, as the standard of care for patients with stage 2 and stage 3 triple-negative breast cancer. 

The trial design is well known. We used what was considered the most effective chemotherapy backbone: 12 weeks of paclitaxel and carboplatin followed by four cycles of EC or AC chemotherapy, given either with pembrolizumab throughout or with placebo. Patients then underwent surgery and, after surgery, continued either pembrolizumab or placebo for another 6 months. The trial enrolled just under 1,200 patients with stage 2 and stage 3 disease.

There were 2 co-primary end points. The short-term end point was pathologic complete response, or pCR, meaning complete disappearance of all invasive cancer at the time of surgery. The long-term end point was event-free survival, or recurrence-free survival. 

We had previously demonstrated that the addition of pembrolizumab to preoperative chemotherapy significantly improved pCR rates. Two years later, we showed that pembrolizumab reduced the risk of recurrence by approximately 35%. Another two years later, we demonstrated that this translated into a significant overall survival benefit. Now, with almost eight years of follow-up, we have the final analysis.

This is a very important milestone because triple-negative breast cancer is an aggressive subtype, and when recurrences occur, they tend to occur early. Most recurrences happen within the first two to three years, and approximately 70% of events are seen during that period. By five years, we have typically observed 90% to 95% of all recurrence events. That's exactly what we now see in the Kaplan-Meier curves from KEYNOTE-522. The curves have flattened over time, and with seven to eight years of follow-up, there is very little change in the overall results.

The addition of pembrolizumab continues to significantly improve event-free survival. In this final analysis, the hazard ratio was 0.68, corresponding to an absolute improvement of approximately 9% in event-free survival at seven years. Importantly, this benefit was consistent across all subgroups. That includes patients who were PD-L1 positive and PD-L1 negative, patients with node-positive and node-negative disease, and even patients with the lowest-risk disease in the study, such as those with T2N0 tumors. I think that is clinically very important.

Looking at overall survival, the final hazard ratio was 0.64. That represents a substantial improvement in overall survival, with an absolute difference of approximately 7% at seven years. Again, the benefit was consistent across all subgroups. 

One of the most interesting preplanned exploratory analyses looked at outcomes according to whether patients achieved a pathologic complete response or had residual disease after neoadjuvant treatment. Two findings stand out. 

First, among patients with residual disease—where one could argue that treatment had not worked optimally—we still observed a substantially better outcome if patients had received chemotherapy plus immunotherapy. At seven years, event-free survival was approximately 10% higher than in patients who received chemotherapy alone. My interpretation is that the addition of immunotherapy clearly changes the biology of the disease. Even when the tumor does not completely disappear, patients still experience a meaningful long-term benefit. 

The second important finding concerns patients who achieved a pathologic complete response. We already know that patients with a pCR generally have an excellent prognosis. However, even among these patients, there was an approximately 4% to 4.5% improvement in seven-year event-free survival with pembrolizumab. This suggests that the quality of a pCR may actually be different when it is achieved with immunotherapy plus chemotherapy compared with chemotherapy alone.  We had seen similar signals previously, but at the time of the earlier overall survival analysis, the data were not mature enough to fully demonstrate this. 

Now, with the final analysis, we see the same pattern not only for event-free survival but also for overall survival. The quality of the pCR appears to be improved with pembrolizumab, and this is now reflected in long-term survival outcomes.

Finally, regarding safety, no new safety signals emerged. The safety profile of pembrolizumab plus chemotherapy is now well established, and clinicians have become increasingly experienced in managing these adverse events. 

In summary, this is the final analysis of a pivotal study that firmly established pembrolizumab plus chemotherapy as the standard of care for patients with stage II and stage III triple-negative breast cancer. The study confirms substantial and clinically meaningful long-term benefits, with a hazard ratio of 0.68 for event-free survival and 0.64 for overall survival. Thank you very much.

Source: 

Schmid P, Cortes J, Dent RA, et al. Neoadjuvant pembrolizumab or placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo for high-risk early-stage TNBC: Final analysis results from the phase 3 KEYNOTE-522 study. Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. Abstract 507.