Pembro Lead-In Lifts ORR to 47% and Extends OS to 26 mo in Metastatic TNBC

In a single-institution Phase II trial (NCT02752685) enrolling 50 patients with metastatic triple-negative breast cancer (TNBC), regardless of PD-L1 status, investigators compared two sequential “run-in” strategies prior to treatment with pembrolizumab (a PD-1 inhibitor) and nab-paclitaxel (a taxane). A chemotherapy lead-in (cTNBC; nab-paclitaxel alone, n = 30) resulted in a 23% ORR, with a mPFS of 5.5 months and a mOS of 18.0 months. In contrast, an immunotherapy lead-in (iTNBC; single-dose pembrolizumab, n = 20) nearly doubled the ORR to 47%, prolonged PFS to 8.4 months (HR 0.68), and extended OS to 25.8 months (HR 0.50,p= 0.043). Pembrolizumab priming converted 31% of initially PD-L1-low tumors to a combined positive score (CPS) ≥ 10, compared to 14% with chemotherapy priming. Additionally, baseline blood ratios—specifically, a higher lymphocyte-to-neutrophil ratio and a lower monocyte-to-lymphocyte ratio—were associated with longer survival. Safety remained manageable across both cohorts.