Peter Schmid, MD, PhD, Barts Cancer Institute, London, England, United Kingdom, presents updated results from the KEYNOTE-522 study. This placebo-controlled, phase 3 study evaluated the addition of pembrolizumab to neoadjuvant chemotherapy with adjuvant pembrolizumab among patients with early stage triple-negative breast cancer.

Dr Schmid concluded this data “show[s] a significant and meaningful improvement in in event-free survival across all subgroups, including the clinically really important subgroup of T2N0 patients.”

Transcript:

I'm Peter Schmid, a medical oncologist who works at Barts Hospital in London. It was my pleasure to present updated result of the KEYNOTE-522 trial in San Antonio. The KEYNOTE-522c trial was the first randomized phase 3 trial of immunotherapy in combination with preoperative chemotherapy, and immunotherapy was also given in the adjuvant setting. The trial was designed for patients with stage 2 or stage 3 untreated triple-negative breast cancer. Patients received 6 months of chemotherapy, 3 months with carboplatin-paclitaxel, 3 months with [adriamycin and cyclophosphamide] AC, either with pembrolizumab or with placebo, then had surgery and continued with pembrolizumab or placebo for another 6 months. The trial had 2 primary end points, a short term end point in terms of pathCR rates, pathologic complete responses, defined at the time of surgery, and the long term end point of event-free survival, so looking at recurrences over time.

We have previously demonstrated that the addition of pembrolizumab significantly increased pathCR rates by about 13.6%, from 51% to nearly 65%. That was significant, and that was meaningful. We'd also previously reported that after 3 years of follow-up, the addition of pembrolizumab led to a significant improvement in event-free survival, hazard ratio of 0.63. We have now 5-year follow-up data, and 5-year follow-up data are really important for triple-negative breast cancer.

We know in triple-negative breast cancer, the majority of recurrences occur relatively early. We see about, probably, 70% of recurrences in the first 3 years. We see probably about 85% to 90% of recurrences in the first 5 years. With 5-year follow-up data, we have robust definitive data in terms of event-free survival. With 63 months of median follow-up, we demonstrated that we have a sustained significant improvement in event-free survival, hazard ratio of 0.63. If you look at the 5-year event free survival rates, they were around 81% for patients who received chemotherapy and pembrolizumab compared to 72% for patients with chemotherapy alone. That's important. That's meaningful. If you look at the event-free survival in subgroups, patients with node-positive disease, node-negative disease, stage 2 diseases, stage 3 disease, we see a very similar benefit. We see a similar delta confirming that the benefit is seen across all subgroups.

We picked one subgroup that's clinically really important. I often get the question in clinic, does every patient with stage 2 or stage 3 disease really need pembrolizumab added to chemotherapy? What about if you have a patient with a 22 millimeter or 23 millimeter triple-negative breast cancer, no lymph node involvement? And to address that question, we looked specifically at the group of patients with T2N0, so tumors between 2 to 5 centimeters and no lymph node involvement. And really reassuringly, we see that the addition of pembrolizumab provides at least the same benefit in this group. We see a hazard ratio of 0.49. We see a 10% better 5-year event-free survival if patients receive chemotherapy and immunotherapy, suggesting that actually all patients with stage 2 and stage 3 disease should be considered for chemotherapy and pembrolizumab.

Another area we looked into was the quality of the responses. As you've known for a long time, the patients who have a complete pathological response have a much better outlook than patients who have residual disease. And so we looked at the outlook of patients who have a pathCR achieved with chemotherapy alone, chemotherapy and pembrolizumab. But what's interesting to see is that there's a 4% difference. There's a 4% better 5-year event-free survival for patients who had pembrolizumab in addition to chemotherapy. The 5-year event-free survival was 92% for chemo and pembrolizumab compared to 88% for chemotherapy alone, and that's the same whether patients are node-positive, node-negative, stage 2 or stage 3 disease.

A third area we focused on in in in the presentation here in San Antonio was brain metastases as a site of disease recurrence. We have obviously demonstrated that we can significantly reduce the incidence of extracranial metastasis, everything outside the brain, but if you look at brain metastases as the first site of event in particular, we see about 2% of patients who receive chemotherapy and pembrolizumab develop brain metastases. About 3% of patients who receive chemotherapy alone develop brain metastases. And when we look at the incidence of brain metastases in patients with residual disease, it remains the same. In other words, we are able to reduce the incidence of extracranial metastases significantly with chemotherapy and with chemotherapy and pembrolizumab, but the incidence of brain metastases remains relatively stable whether patients responded well or not. That's important, but knowing that the incidence is only 2%, it’s probably not required to develop specific strategies for those patients.

In summary, what represented in San Antonio is robust, definitive 5-year follow-up data. We show a significant and meaningful improvement in in event-free survival across all subgroups, including the clinically really important subgroup of T2N0 patients. We were hoping to share overall survival data, but this is an event driven analysis and we haven't seen the required events, which I suppose is a really positive thing, supporting further that we improve outcomes of patients with the addition of pembrolizumab to chemotherapy. Thank you very much.

Source:

Schmid P, Cortés J, Dent R, et al. Neoadjuvant pembrolizumab or placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo for early-stage triple-negative breast cancer: Updated event-free survival results from the phase 3 KEYNOTE-522 study. Presented at San Antonio Breast Cancer Symposium; December 5-9, 2023; San Antonio, Texas. Abstract LBO1-01