Pembrolizumab offers survival benefits in early-stage TNBC

Neoadjuvant pembrolizumab plus chemotherapy improves event-free survival (EFS) in high-risk, early-stage triple-negative breast cancer (TNBC) patients with residual cancer burden (RCB), suggests a study.

A team of investigators randomized 1,174 patients with stage T1c/N1-2 or T2-4/N0-2 TNBC in a 2:1 ratio to receive either pembrolizumab 200 mg or placebo every 3 weeks, given with four cycles of paclitaxel plus carboplatin, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide.

Patients received pembrolizumab or placebo for nine cycles or until recurrence or unacceptable toxicity following surgery. Pathological complete response (pCR) and EFS were the primary endpoints, while RCB was a prespecified exploratory endpoint. A Cox regression model was used to explore the relationship between EFS and RCB.

Neoadjuvant pembrolizumab plus chemotherapy moved patients into lower RCB categories across the entire spectrum relative to placebo. The pembrolizumab group had more patients with RCB-0 and fewer patients with RCB-1, RCB-2, and RCB-3.

The hazard ratios for EFS were 0.70 (95 percent confidence interval [CI], 0.38‒1.31) for RCB-0, 0.92 (95 percent CI, 0.39‒2.20) for RCB-1, 0.52 (95 percent CI, 0.32‒0.82) for RCB-2, and 1.24 (95 percent CI, 0.69‒2.23) for RCB-3.

Distant recurrences were the most common first EFS event, and these were fewer in the pembrolizumab group across all RCB categories. Among patients in the RCB-0/1 class, 21 (55.3 percent) had central nervous system recurrences: 13 of 22 (59.1 percent) in the pembrolizumab group and eight of 16 (50.0 percent) in the placebo group.

“[The] addition of pembrolizumab to chemotherapy resulted in fewer EFS events in the RCB-0, RCB-1, and RCB-2 categories, with the greatest benefit in RCB-2,” the investigators said. “These findings demonstrate that pembrolizumab not only increased pCR rates, but also improved EFS among most patients who do not have a pCR.”