Dr. Costa on the Efficacy of Neoadjuvant Pembrolizumab Plus Chemotherapy in Early-Stage TNBC

Ricardo Costa, MD, MSC, a medical oncologist in thhe Department of Breast Oncology at Moffitt Cancer Center, discusses the use of neoadjuvant pembrolizumab (Keytruda) plus chemotherapy, followed by adjuvant pembrolizumab monotherapy, in patients with high-risk, early-stage triple-negative breast cancer (TNBC).

In July 2021, the FDA approved pembrolizumab for the treatment of patients with high-risk, early-stage TNBCin combination with chemotherapy as neoadjuvant treatment, followed by a single-agent adjuvant treatment after surgery, based on data from the phase 3 KEYNOTE-522 trial (NCT03036488).

The phase 3 trial randomly assigned 1174 patients in a 2:1 fashion to receive neoadjuvant chemotherapy with or without pembrolizumab. Chemotherapy consisted of 4 cycles of carboplatin plus paclitaxel, which was followed by 4 cycles of doxorubicin or epirubicin plus cyclophosphamide. Those in the pembrolizumab arm continued with pembrolizumab monotherapy after surgery for 9 cycles, or until patients experienced progression or unacceptable toxicity. The trial enrolled patients with both node-negative and -positive disease. Tumor stage ranged from T1c N1/N2 to T2 to T4 and N0 to N2, per AJCC criteria.

In a previously reported data on the trial’s co-primary end points, the pathological complete response rate was 64.8% for patients treated in the pembrolizumab arm, compared with 51.2% for those in the chemotherapy alone arm.

Additionally, the estimated 3-year event-free survival was 84.5% in those treated with pembrolizumab plus chemotherapy, compared with 76.8% for those treated with chemotherapy alone. At a median follow-up of 39.0 months, the pembrolizumab regimen resulted in a 37% reduction in the risk of disease progression that precluded definitive surgery, a local/distant recurrence, a second primary cancer, or death from any cause (HR, 0.63; 95% CI, 0.48-0.82; P = .00031).

These data continue to support the use of neoadjuvant pembrolizumab plus chemotherapy, followed by adjuvant pembrolizumab, for patients with high-risk, early-stage TNBC, Costa concludes.