As reported in The Lancet Oncology by Eric P. Winer, MD, FASCO, and colleagues, the phase III KEYNOTE-119 trial showed no significant improvement in overall survival with pembrolizumab vs investigator’s choice of chemotherapy in the second- or third-line treatment of metastatic triple-negative breast cancer. Evidence of potential pembrolizumab benefit was observed in patients with a higher tumor PD-L1 combined positive score (CPS).

Pembrolizumab did not significantly improve overall survival in patients with previously treated metastatic triple-negative breast cancer vs chemotherapy. These findings might inform future research of pembrolizumab monotherapy for selected subpopulations of patients … and inform a combinatorial approach for the treatment of patients with metastatic triple-negative breast cancer.

— Eric P. Winer, MD, FASCO, and colleagues

Tweet this quote

Study Details

The open-label trial included 662 patients from sites in 31 countries who had received one or two previous systemic treatments for metastatic disease and had previous treatment with an anthracycline or taxane. Patients were randomly assigned between November 2015 and April 2017 to receive pembrolizumab at 200 mg once every 3 weeks for 35 cycles (n = 312) or investigator’s choice of single-agent chemotherapy with capecitabine, eribulin, gemcitabine, or vinorelbine (60% enrollment cap for each; n = 310).

Primary endpoints were overall survival in patients with a PD-L1 CPS ≥ 10, those with CPS ≥ 1, and all patients in the intention-to-treat population. Superiority of pembrolizumab vs chemotherapy was tested in all patients only if superiority was shown in those with CPS ≥ 1.

Overall Survival

Median follow-up was 31.4 months (interquartile range [IQR] = 27.8–34.4 months) in the pembrolizumab group and 31.5 months (IQR = 27.8–34.6 months) in the chemotherapy group.

Among 96 patients (31%) vs 98 patients (32%) with CPS ≥ 10, median overall survival was 12.7 months (95% confidence interval [CI] = 9.9–16.3 months) in the pembrolizumab group vs 11.6 months (95% CI = 8.3–13.7 months) in the chemotherapy group (hazard ratio [HR] = 0.78, 95% CI = 0.57–1.06, P = .057). Among 203 patients (65%) vs 202 patients (65%) with CPS ≥ 1, median overall survival was 10.7 months (95% CI = 9.3–12.5 months) in the pembrolizumab group vs 10.2 months (95% CI = 7.9–12.6 months) in the chemotherapy group (HR = 0.86, 95% CI = 0.69–1.06, P = .073). In the overall population, median overall survival was 9.9 months (95% CI = 8.3–11.4 months) vs 10.8 months (95% CI = 9.1–12.6 months; HR = 0.97, 95% CI = 0.82–1.15).

In an exploratory post hoc analysis, among 57 patients (18%) vs 52 patients (17%) with CPS ≥ 20, median overall survival was 14.9 months (95% CI = 10.7–19.8 months) in the pembrolizumab group vs 12.5 months (95% CI = 7.3–15.4 months) in the chemotherapy group (HR = 0.58, 95% CI = 0.38–0.88).

Objective response rates were 12% vs 9% among patients with CPS ≥ 1, 18% vs 9% among those with CPS ≥ 10, and 26% vs 12% among those with CPS ≥ 20.

Adverse Events

Grade 3 to 4 treatment-related adverse events occurred in 14% of patients in the pembrolizumab group vs 36% of the chemotherapy group, with the most common being anemia (1% vs 3%), decreased white blood cells (< 1% vs 5%), decreased neutrophil count (< 1% vs 10%), and neutropenia (0% vs 13%). Serious adverse events occurred in 20% vs 20% of patients, with the most common being pleural effusion (2% vs 1%), pneumonia (2% vs 2%), and febrile neutropenia (< 1% vs 2%).

Immune-mediated adverse events occurred in 15% vs 3% of patients, with the most common in the pembrolizumab group being hypothyroidism (7.8%). Adverse events led to death in one patient (< 1%) in the pembrolizumab group (due to circulatory collapse) and in two patients (1%) in the chemotherapy group (due to pancytopenia and sepsis in 1 and hemothorax in 1).

The investigators concluded, “Pembrolizumab did not significantly improve overall survival in patients with previously treated metastatic triple-negative breast cancer vs chemotherapy. These findings might inform future research of pembrolizumab monotherapy for selected subpopulations of patients, specifically those with PD-L1–enriched tumors, and inform a combinatorial approach for the treatment of patients with metastatic triple-negative breast cancer.”

Dr. Winer, of the Division of Breast Oncology, Dana-Farber Cancer Institute, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Merck Sharp & Dohme. For full disclosures of the study authors, visit thelancet.com.