ASCO 2026 | KEYNOTE-522: final analysis of pembrolizumab and chemotherapy in TNBC

The chemo 5-2 trial is a pivotal study in early stage triple negative breast cancer. It really established pembrolizumab as the standard of care for those patients, given first together with neo-adjuvant chemotherapy and then continued post-operatively as adjuvant therapy for another six months. The trial included patients with stage 2 and 3 disease. It had two primary endpoints, short-term readout with pCR, complete pathological response, and then the long-term endpoint with event-free survival. The chemotherapy regimen selected is what I would describe as the most effective chemotherapy regimen. We have at the moment 12 weeks of weekly paclitaxel and carboplatin, and then 12 weeks of EC or AC chemotherapy, either with pembrolizumab or placebo all the way through, then surgery, and then continuation with pembrolizumab or placebo. Now, we have previously, a few years ago, actually, that the trial met its first primary endpoint in terms of pCR rates, improving pCR rates significantly with the addition of Pembrolizumab. Then a couple of years later, we showed for the first time that the addition of Pembrolizumab improved the event-free survival rate at that time with a hazard ratio of 0.65. And then another two years later, we demonstrated that this led to an overall survival benefit. Now, here we presented a long-term follow-up update. This is the final analysis ever for Keynote 522, which is important as it’s such a pivotal study. And the trial data obviously confirmed what we had seen before with longer follow-up. That’s not surprising because most of the events in triple-negative breast cancer happened relatively early, after two to three years, maximum after five years. So the data are now very, very stable. We demonstrated that the event-free survival rates are 0.68. That’s about a 9%, just under 10% delta in the seven-year event-free survival rates. Equally, for overall survival, we demonstrated a hazard ratio of 0.64. Again, very stable rates with about 8% delta. The benefits of pembrolizumab were consistent across all clinical subgroups. That’s really important. So that includes node-negative patients. That includes smaller tumors. Even the smallest disease group with T2N0 had a very substantial benefit. But it also includes patients regardless of the PD-L1 status. PD-L1 negative and PD-L1 positive patients derived a very comparable benefit. But it also includes patients, regardless of the PD-L1 status, PD-L1 negative or PD-L1 positive patients, derived a very comparable benefit. We also did an analysis in this trial and updated this now for the final analysis, looking at the outcome of patients depending on the response. So the data were separated by pCR, pathological complete response, and patients who had residual disease. And really interesting two observations. Patients who have residual disease have a substantially better outcome. If this happened after treatment with chemotherapy and immune therapy, suggesting that pembrolizumab changes their biology, the delta was about 10% in absolute terms. That’s a big difference. But equally interesting in patients who had a complete response, where we know they have a fantastic outcome, the delta is about 4% better, so a 4% lower recurrence rate for patients who had a pathologically complete response after chemotherapy and pembrolizumab compared to chemotherapy alone. Now, when we previously reported those data, we saw this only event-free survival, but not yet in overall survival. Now, with long-term follow-up of nearly eight years, we also see there is a different outcome in overall survival in patients with a pathologic complete response if it was achieved together with Pembrolizumab. Looking at the final safety data, there are no new signals emerging. The safety of Pembrolizumab in combination with chemotherapy has been well described. So in summary, the long-term and final data of Keynote 522 confirmed what we know. This is a pivotal study that has led to the approval of Pembrolizumab in this treatment setting exactly in this way, giving neoadjuvantly and then continued after surgery and substantially reduces the risk of recurrence by about 32%, but also improves survival by about 36%. Thank you very much.

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