A perioperative regimen of pembrolizumab plus chemotherapy has demonstrated a statistically significant improvement in overall survival (OS) compared to chemotherapy plus placebo in patients with early-stage triple-negative breast cancer (TNBC). The findings, presented at the 2024 ESMO Congress from the phase 3 KEYNOTE-522 trial, highlight a substantial advancement in the treatment of this aggressive form of breast cancer.
The KEYNOTE-522 trial (NCT03036488) revealed that the pembrolizumab regimen reduced the risk of death by 34% compared with the placebo regimen (HR, 0.66; 95% CI, 0.50-0.87; P = .00150). After a median follow-up of 75.1 months, the 5-year OS rate was 86.6% (95% CI, 84.0%-88.8%) in the pembrolizumab arm (n = 784) compared to 81.7% (95% CI, 77.5%-85.2%) in the placebo arm (n = 390). The OS event rates were 14.7% and 21.8% for the pembrolizumab and placebo arms, respectively.
Keynote-522 Design and Efficacy
The KEYNOTE-522 trial is a randomized, double-blind study involving patients with centrally confirmed TNBC. Eligible patients had newly diagnosed, previously untreated, nonmetastatic disease, defined as tumor stage T1c, nodal stage N1-2, or tumor stage T2-4, nodal stage N0-2. Patients were randomized 2:1 to receive either pembrolizumab or placebo. The neoadjuvant setting involved pembrolizumab (200 mg) or placebo every 3 weeks for 4 cycles, plus paclitaxel (80 mg/m2) weekly and carboplatin (AUC of 5 mg/mL per minute every 3 weeks or 1.5 mg/mL per minute weekly) for the first 12 weeks. This was followed by pembrolizumab or placebo for 4 additional cycles, plus doxorubicin (60 mg/m2) or epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) every 3 weeks for 12 weeks.
In the adjuvant setting, patients received pembrolizumab or placebo every 3 weeks for up to 9 cycles. Radiation was permitted. The dual primary endpoints were pathological complete response (pCR) rate and event-free survival (EFS) in the intention-to-treat population. Secondary endpoints included pCR and EFS in patients with PD-L1–positive tumors, and OS among all patients and those with PD-L1–positive tumors.
Impact of pCR on Survival
Patients who achieved a pCR on the study also experienced an OS benefit, irrespective of the treatment arm. In responders, the 5-year OS rate was 95.1% for the pembrolizumab arm (n = 495) vs 94.4% for the placebo arm (n = 217; HR, 0.69; 95% CI, 0.38-1.26). For non-responders, the 5-year OS rate was 71.8% for the pembrolizumab arm (n = 289) vs 65.7% for the placebo arm (n = 173; HR, 0.76; 95% CI, 0.56-1.05).
"[KEYNOTE-522] was a positive trial for its 2 primary end points—short-term pathological complete response [(pCR) rate] and event-free survival [EFS]—and most importantly, [data] demonstrated that [the pembrolizumab regimen] reduced the risk of death by 34%," said lead study author Peter Schmid, MD, PhD, of Barts Cancer Institute at Queen Mary University in London, United Kingdom, during a press briefing at the ESMO Congress.
Previous Findings
Previously reported data from the first interim analysis of KEYNOTE-522 at a median follow-up of 15.5 months showed that patients in the pembrolizumab arm achieved a pathological complete response (pCR) rate of 64.8% (95% CI, 59.9%-69.5%) compared with 51.2% (95% CI, 44.1%-58.3%) those in the placebo arm (estimated difference, 13.6%; 95% CI, 5.4%-21.8%; P < .001).
