Results from KEYNOTE-B49: A phase 3, randomized, double-blind study of pembrolizumab (pembro) vs placebo (pbo) plus chemotherapy (CT) in participants (pts) with HR+/HER2− advanced breast cancer (ABC)

doi:10.1016/j.annonc.2026.10.1285

KEYNOTE-B49

Patient / Population Intervention / Exposure Comparison Outcome

In patients with PD-L1 CPS ≥1 HR+/HER2− advanced breast cancer after endocrine therapy, pembrolizumab plus chemotherapy improved progression-free survival but not overall survival compared with placebo plus chemotherapy.

N

342patients

Design

Phase 3, randomised, double-blind, placebo-controlled trial of pembrolizumab vs placebo, each plus investigator-chosen chemotherapy (paclitaxel, nab-paclitaxel, liposomal doxorubicin or capecitabine), in patients with locally recurrent inoperable or metastatic HR+/HER2- breast cancer with PD-L1 CPS ≥1 who had prior endocrine therapy and were candidates for first-line chemotherapy (NCT04895358).

Endpoint

Progression-free survival per RECIST v1.1 by blinded independent central review in patients with PD-L1 CPS ≥1.

ResultAt the primary analysis (median follow-up 29.1 months), median progression-free survival was 6.7 months (95% CI 6.2-8.3) with pembrolizumab plus chemotherapy vs 6.0 months (95% CI 4.2-8.1) with placebo plus chemotherapy (HR 0.74; 95% CI 0.58-0.95; P = 0.0089), with 124/171 vs 139/171 events. In patients with PD-L1 CPS ≥10, median progression-free survival was 7.5 vs 4.4 months (HR 0.59; 95% CI 0.35-0.98). At the final analysis (median follow-up 34.9 months), the progression-free survival benefit was maintained (HR 0.74; 95% CI 0.58-0.95), but median overall survival was 21.0 vs 22.2 months (HR 1.04; 95% CI 0.81-1.33; P = 0.6185). Grade ≥3 treatment-related adverse events occurred in 37.6% vs 32.7%, and 11.2% vs 5.4% discontinued treatment because of treatment-related adverse events.

Rugo H, Kok M, Goncalves A, et al. Annals of Oncology. 2026. 10.1016/j.annonc.2026.10.1285

Discussion & critique

This double-blind trial met its primary endpoint, but the gain in median progression-free survival was small (6.7 vs 6.0 months) and did not translate into an overall survival benefit at the final analysis (HR 1.04). The sample size was cut by a protocol amendment because PD-L1 positivity was uncommon. The stronger effect in the CPS ≥10 subgroup is a numerical finding with a wide confidence interval, not a tested result. The abstract does not report response rates, quality of life or immune-related adverse events, and more patients stopped treatment because of toxicity on the pembrolizumab arm.