Pembrolizumab Plus Chemotherapy for HR+/HER2- PD-L1‒Positive Advanced Breast Cancer: Final Analysis of the Phase 3 KEYNOTE-B49 Study.
Abstract
Background
We evaluated pembrolizumab plus chemotherapy versus chemotherapy alone in participants with PD-L1‒positive, hormone receptor-positive (HR+)/HER2- advanced breast cancer after progression on prior endocrine-based therapy (ET). PATIENTS AND
Methods
Participants with locally recurrent inoperable or metastatic HR+/HER2- breast cancer with PD-L1 combined positive score (CPS) ≥1 who had prior ET and were candidates for first-line chemotherapy were randomized to pembrolizumab 200 mg or placebo Q3W plus chemotherapy. The primary and key secondary endpoints were progression-free survival (PFS) per RECIST v1.1 by blinded independent central review and overall survival (OS), respectively, in participants with PD-L1 CPS ≥1. PFS and OS in participants with PD-L1 CPS ≥10 and safety were secondary endpoints. Following protocol amendment, the sample size was reduced due to low PD-L1 prevalence.
Results
342 participants were randomized. At interim analysis (median follow-up, 29.1 months), the hazard ratio (HR) for PFS was 0.74 (95% CI, 0.58‒0.95; P=0.0089 [significance criterion met]) favoring pembrolizumab plus chemotherapy versus placebo plus chemotherapy (median [95% CI] PFS, 6.7 [6.2‒8.3] versus 6.0 [4.2‒8.1] months). HR for PFS in participants with PD-L1 CPS ≥10 numerically favored pembrolizumab plus chemotherapy (0.59; 95% CI, 0.35‒0.98). At final analysis (median follow-up, 34.9 months), HR for OS was 1.04 (95% CI, 0.81‒1.33; P=0.6185) for pembrolizumab plus chemotherapy versus placebo plus chemotherapy (median [95% CI] OS, 21.0 [18.9‒22.9] versus 22.2 [17.6‒26.3] months). Grade ≥3 treatment-related AEs occurred in 38% of participants in the pembrolizumab plus chemotherapy arm and 33% in the placebo plus chemotherapy arm; 11% and 5% discontinued treatment due to treatment-related AEs, respectively.
Conclusion
In participants with PD-L1‒positive (CPS ≥1) HR+/HER2- advanced breast cancer, pembrolizumab plus chemotherapy demonstrated statistically significant improvement in PFS, with no new safety signals observed. A numerical effect favoring pembrolizumab plus chemotherapy for PFS was observed in participants with PD-L1 CPS ≥10. No significant OS improvement was observed. CLINICAL TRIAL REGISTRATION KEYNOTE-B49; ClinicalTrials.gov, NCT04895358.