Dr Ademuyiwa on the Implications of the KEYNOTE-522 Trial in Early-Stage TNBC

Foluso Bisi Ademuyiwa, MD, MPH, MSCI, associate professor of medicine, Division of Oncology, Section of Breast Oncology, the Washington University School of Medicine, discusses the implications of the phase 3 KEYNOTE-522 trial (NCT03036488) in high-risk, early-stage triple-negative breast cancer (TNBC).

Results from the study supported the July 2021 FDA approval of pembrolizumab in combination with chemotherapy as neoadjuvant therapy, with pembrolizumab continued as a single agent as adjuvant treatment following surgery, in patients with high-risk, early-stage TNBC.

KEYNOTE-522 represented one of the key clinical trials that shifted the treatment paradigm for patients with early-stage TNBC, Ademuyiwa begins. This study randomly assigned previously untreated patients with stage II or stage III TNBC to receive pembrolizumab plus carboplatin and paclitaxel, or placebo plus carboplatin and paclitaxel. Findings showed that patients who received pembrolizumab plus experienced a higher pathological complete response (pCR) rate (64.8%) compared with patients who received placebo plus chemotherapy (51.2%). Moreover, the 3-year event free survival rate was 84.5% for patients treated with pembrolizumab plus chemotherapy, compared with 76.8% for those given chemotherapy alone.

Most recently, investigators revealed that the addition of pembrolizumab to chemotherapy also provided a benefit for a subset of patients who had extensive residual disease and experienced distant recurrences, Ademuyiwa continues. These patients with extensive residual disease had worse outcome compared with patients who achieved a pCR; however, there was still a tangible benefit from the addition of pembrolizumab to neoadjuvant chemotherapy.

Given the findings of KEYNOTE-522, patients with clinical stage II/III TNBC should be offered neoadjuvant chemotherapy in combination with pembrolizumab, Ademuyiwa notes. Additionally, pembrolizumab should be continued for at least 1 year, even if patients do not achieve a pCR, because these patients can still derive a benefit with that addition of pembrolizumab, Ademuyiwa concludes.