Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab improved outcomes, compared with chemotherapy alone, in patients with high-risk, early triple-negative breast cancer (TNBC), according to results of the KEYNOTE-522 trial.

These results were presented at a European Society for Medical Oncology (ESMO) Virtual Plenary by Peter Schmid, MD, PhD, of Cancer Research UK Barts Centre in London, England.

The phase 3 KEYNOTE-522 trial ( Identifier: NCT03036488) enrolled adults with newly diagnosed, high-risk TNBC. A total of 1174 patients were randomly assigned 2:1 to receive neoadjuvant pembrolizumab plus chemotherapy (n=784) or placebo plus chemotherapy (n=390).

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The chemotherapy consisted of carboplatin plus paclitaxel for the first 4 cycles, followed by doxorubicin, epirubicin, and cyclophosphamide for the second 4 cycles.

After surgery, patients in the pembrolizumab arm received adjuvant pembrolizumab for 27 weeks, and the placebo group continued with placebo.

At baseline, the median age was 49 years in the pembrolizumab arm and 48 years in the placebo arm. Most patients (83.7% and 81.3%, respectively) had PD-L1-positive disease. Approximately half of patients (51.7% and 51.3%, respectively) had nodal involvement.

Pembrolizumab improved both pathologic complete response (pCR) rates and event-free survival (EFS), the co-primary endpoints. The pCR rate was 64.8% in the pembrolizumab arm and 51.2% in the placebo arm (P =.00055).

At 18 months, the EFS rate was 91.3% in the pembrolizumab arm and 85.3% in the placebo arm (hazard ratio [HR], 0.63; 95% CI, 0.43-0.93; P =.0089). At 36 months, the EFS rate was 84.5% and 76.8%, respectively (HR, 0.63; 95% CI, 0.48-0.82; P =.00031).

Pembrolizumab also improved distant progression- or distant recurrence-free survival. At 36 months, the rate was 87.0% in the pembrolizumab arm and 80.7% in the placebo arm (HR, 0.61; 95% CI, 0.46-0.82).

The overall survival (OS) data were not mature at last follow-up. However, the 36-month OS rate was 89.7% in the pembrolizumab arm and 86.9% in the placebo arm (HR, 0.72; 95% CI, 0.51-1.02; P =.03214).

Grade 3-5 treatment-related adverse events (AEs) occurred in 77.1% of patients in the pembrolizumab arm and 73.3% of those in the placebo arm. Grade 3-5 immune-mediated AEs occurred in 14.9% and 2.1%, respectively.

Treatment-related AEs resulted in treatment discontinuation in 27.7% of patients in the pembrolizumab arm and 14.1% of patients in the placebo arm.

“These data clearly support that pembrolizumab plus platinum-containing neoadjuvant chemotherapy, followed by adjuvant pembrolizumab after surgery, should be a new standard-of-care treatment regimen for patients with high-risk, early-stage triple-negative breast cancer,” Dr Schmid said.

Disclosures: This research was supported by Merck Sharp & Dohme Corp. Dr Schmid disclosed relationships with Merck and other companies. Please see the original reference for a full list of disclosures.


Schmid P. KEYNOTE-522: Phase III study of neoadjuvant pembrolizumab + chemotherapy vs. placebo + chemotherapy, followed by adjuvant pembrolizumab vs. placebo for early-stage TNBC. Presented at: ESMO Virtual Plenary. July 15-16, 2021.