Pembrolizumab Delays Progression in Advanced Breast Cancer

ADDING pembrolizumab to chemotherapy extends progression-free survival in advanced breast cancer after any prior endocrine therapy. Findings from the Phase 3 KEYNOTE-B49 trial demonstrate a statistically significant reduction in disease progression or death among patients presenting with hormone receptor-positive, HER2-negative, programmed cell death ligand 1-positive metastatic tumors. Investigators randomized 342 participants who previously experienced progression on endocrine regimens, predominantly including cyclin-dependent kinase 4 and 6 inhibitors, to receive either pembrolizumab or placebo in combination with physician-choice chemotherapy consisting of capecitabine, paclitaxel, nab-paclitaxel, or liposomal doxorubicin.

At the protocol-specified interim analysis, the addition of pembrolizumab reduced the relative risk of disease progression or death by 26 percent compared with chemotherapy alone, achieving a hazard ratio of 0.74. Median progression-free survival reached 6.7 months in the experimental arm versus 6.0 months in the control group. Furthermore, twelve-month progression-free survival rates were 26 percent with the checkpoint inhibitor compared with 20 percent without it, widening at 24 months to 15 percent versus 4 percent. Patients harboring tumors enriched for higher biomarker expression, defined by a combined positive score of 10 or greater, experienced a numerically greater progression-free survival advantage, posting a median of 7.5 months and an unstratified hazard ratio of 0.59.

Evaluating Survival and Safety in Advanced Breast Cancer

Final overall survival assessments showed no statistically significant difference between the two therapeutic cohorts. The median overall survival reached 21.0 months with the immunotherapy combination compared to 22.2 months with chemotherapy alone, generating a hazard ratio of 1.04. Subsequent therapeutic interventions, including widespread administration of antibody-drug conjugates following study treatment discontinuation, occurred in a substantial majority of participants and likely confounded long-term survival metrics.

The safety profile aligned with previously documented experiences for the individual agents without newly identified toxicities. Grade 3 or higher treatment-related adverse events occurred in 38 percent of participants receiving pembrolizumab plus chemotherapy compared with 33 percent receiving chemotherapy alone. Discontinuation of any study agent due to treatment-related adverse events occurred in 11 percent of patients in the combination arm and 5 percent in the placebo cohort. Immune-mediated adverse events occurred in 37 percent of combination recipients, most frequently involving endocrine or pulmonary toxicities. Overall, the trial establishes modest progression-free benefits when introducing immune checkpoint blockade into pretreated advanced breast cancer management.

Reference

Rugo HS et al. Pembrolizumab Plus Chemotherapy for HR+/HER2- PD-L1-Positive Advanced Breast Cancer: Final Analysis of the Phase 3 KEYNOTE-B49 Study. Ann Oncol. 2026; doi: 10.1016/j.annonc.2026.10.1285.