The addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab yielded a statistically significant and clinically meaningful improvement in overall survival (OS) vs neoadjuvant chemotherapy alone for patients with high-risk, early-stage triple-negative breast cancer, according to results from the phase 3 KEYNOTE-522 trial.

In a previous analysis of KEYNOTE-522, the addition of pembrolizumab to chemotherapy showed improvements in pathologic complete response (pCR) and event-free survival (EFS) in this patient population. These updated OS results were presented by Peter Schmid, MD, PhD, Barts Cancer Institute, London, United Kingdom, at the 2024 ESMO Congress in Barcelona, Spain.

The KEYNOTE-522 trial enrolled patients with previously untreated, non-metastatic, centrally confirmed triple-negative breast cancer who were stage T1c N1-2 or T2-4 N0-2 per AJCC. Patients were randomized in a 2:1 ratio to receive neoadjuvant pembrolizumab at 200 mg every 3 weeks or placebo, both given with 4 cycles of paclitaxel plus carboplatin, then 4 cycles of doxorubicin or epirubicin plus cyclophosphamide. After definitive surgery, patients received adjuvant pembrolizumab or placebo for 9 cycles until recurrence or unacceptable toxicity.

The coprimary end points of the trial are pCR and EFS, defined as time from randomization to disease progression that prevented definitive surgery, local/distant recurrence, second primary cancer, or death from any cause. OS is the secondary end point.

A total of 1174 patients were enrolled and randomized to pembrolizumab (n = 784) or placebo (n = 390). At the data cutoff date of March 22, 2024, the median follow-up was 75.1 months (range, 65.9 to 84). Overall, 115 (14.7%) patients in the pembrolizumab group and 85 (21.8%) patients in the placebo group had died (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.50 to 0.87; P = .0015), meting the prespecified significance boundary of 0.00503.

The 5-year OS rate was 86.6% (95% CI, 84 to 88.8) in the pembrolizumab arm vs 81.7% (95% CI, 77.5 to 85.2) in the placebo arm.  The 5-year EFS rate was 81.2% (95% CI, 78.3 to 83.8) vs 72.2% (95% CI, 67.4 to 76.4), respectively (HR, 0.65; 95% CI, 0.51 to 0.83).

Grade ≥3 treatment-related adverse events (AEs) occurred in 77.1% of patients in the pembrolizumab arm and 73.3% in the placebo arm (death incidence, 0.5% vs 0.3%, respectively). Immune-mediated AEs of any grade occurred in 35% vs 13.1% of patients in each group, respectively.

In conclusion, the KEYNOTE-522 trial demonstrated a statistically significant and clinically meaningful improvement in OS with the addition of pembrolizumab to neoadjuvant chemotherapy for patients with high-risk, early-stage triple-negative breast cancer.

Source:

Schmid P, Cortes J, Dent RA, et al. Neoadjuvant pembrolizumab or placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo for high-risk early-stage TNBC: Overall survival results from the phase III KEYNOTE-522 study. Presented at 2024 ESMO Congress. September 13-17, 2024. Abstract LBA4