Pembrolizumab Is a New Standard for Early-Stage TNBC

Standard of care options for patients with early-stage triple-negative breast cancer (TNBC) include neoadjuvant chemotherapy to improve pathological complete response (pCR) rate and, ultimately, event-free survival (EFS). If improved pCR rates do not translate into improved long-term clinical outcomes, however, the validity of this approach could be legitimately questioned. With clinical trials showing the benefit of immunotherapy in selected patients with metastatic TNBC, it was a natural progression to evaluate its role in patients with earlier stage disease.

Previous interim analyses from the KEYNOTE-522 trial in patients with previously untreated stage II or III TNBC confirmed that the addition of pembrolizumab to neoadjuvant chemotherapy significantly increased pCR rate, from 51% to 65%, but they did not show a statistically significant improvement in EFS. Now, in the fourth planned interim analysis of KEYNOTE-522, investigators report EFS at 36 months.

In the phase 3, industry-funded trial, 1174 patients were randomized to receive neoadjuvant therapy with pembrolizumab or placebo every 3 weeks plus paclitaxel and carboplatin for four cycles, followed by pembrolizumab or placebo plus cyclophosphamide plus doxorubicin or epirubicin for four cycles. Following definitive surgery, patients received adjuvant pembrolizumab or placebo every three weeks for up to nine cycles. The primary endpoints were pCR rate and EFS.

At the time of this analysis, median duration of follow-up was 39.1 months. The estimated EFS at 36 months was significantly higher in the pembrolizumab–chemotherapy group than in the placebo–chemotherapy group (84.5% vs. 76.8%). Overall survival (OS) data were immature, but the estimated OS at 36 months did not differ significantly between the two groups (89.7% and 86.9%). No new safety signals were detected.