Pembrolizumab Plus Chemotherapy Improves OS vs Chemotherapy and Placebo in Advanced Triple-Negative Breast Cancer

Pembrolizumab plus chemotherapy for advanced triple-negative breast cancer was associated with prolonged overall survival (OS) vs chemotherapy plus placebo in patients with tumors expressing programmed death ligand 1 (PD-L1) and a combined positive score (CPS) ≥10 compared to chemotherapy plus placebo, according to final analysis of findings from a phase 3 trial.

For patients with triple-negative breast cancer, “chemotherapy results in suboptimal antitumor response rates and short overall survival and response durations,” wrote Javier Cortes, MD, PhD, International Breast Cancer Center, Pangaea Oncology, Quirónsalud Group, Barcelona, Spain, and colleagues. “New therapeutic strategies to improve outcomes are needed.”

The phase 3 KEYNOTE-355 trial enrolled 847 patients with previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer. Patients were randomly assigned in a 2:1 ratio to receive either 200 mg intravenous pembrolizumab every 3 weeks plus chemotherapy (n = 566) or chemotherapy plus placebo (n = 281). The primary end point in this final analysis of results was overall survival (OS) in patients in the CPS-10 and CPS-1 (tumors expressing PD-L1 with a CPS≥10 and ≥1, respectively) subgroups, and patients in the intention-to-treat population. Final analysis also sought to assess treatment safety.

After a median follow-up of 44.1 months, patients in the CPS-10 subgroup experienced a median OS of 23 and 16.1 months with pembrolizumab plus chemotherapy vs chemotherapy plus placebo, respectively (hazard ratio [HR] for death 0.73; 95% confidence interval [CI], 0.55 to 0.95; two-sided P = .0185), which met the criterion for significance. Among CPS-1 subgroup patients, median OS was 17.6 months in the pembrolizumab plus chemotherapy arm and 16 months in the chemotherapy plus placebo arm (HR 0.86; 95% CI, 0.72 to 1.04; two-sided P = .1125), which did not meet the criterion for significance. For all patients treated with pembrolizumab plus chemotherapy, the median OS was 17.2 compared to 15.5 months for those treated with chemotherapy plus placebo, (HR 0.89; 95% CI, P = .76 to 1.05 [significance not tested]).

Patients experienced adverse events grade ≥3 whether treated with pembrolizumab plus chemotherapy or chemotherapy plus placebo (68.1% vs 66.9%). There were no deaths reported in the chemotherapy plus placebo arm, and 2 reported in the pembrolizumab plus chemotherapy arm (1 due to acute kidney injury and 1 due to pheumonia).

Dr Cortes et al concluded, “Together with similar observations in studies of atezolizumab for metastatic and early triple-negative breast cancer, these observations suggest a differential role of baseline tumor PD-L1 expression in the efficacy of immune-checkpoint inhibition for early-stage as compared with late-stage disease.”

Source:                                        

Cortes J, Rugo HS, Cescon DW, et al. Pembrolizumab plus Chemotherapy in Advanced Triple-Negative Breast Cancer. N Engl J Med. 2022;387(3):217-226. doi:10.1056/NEJMoa2202809