Outcomes with pembrolizumab (pembro) monotherapy in patients (pts) with PD-L1–positive NSCLC with brain metastases: Pooled analysis of KEYNOTE-001, -010, -024, and -042

Abstract

Background: Prognosis is historically poor for pts with NSCLC with brain metastases. We present a pooled analysis from 4 clinical trials that evaluated outcomes in pts with PD-L1-positive NSCLC with stable brain metastases at baseline treated with pembro vs chemotherapy (chemo). Methods: This post hoc analysis pooled data for pts with previously treated or untreated PD-L1-positive (PD-L1 TPS ≥1%) advanced NSCLC in KEYNOTE-001 (NCT01295827), KEYNOTE-010 (NCT01905657), KEYNOTE-024 (NCT02142738), and KEYNOTE-042 (NCT02220894) assigned to pembro (2 mg/kg, 10 mg/kg, or 200 mg Q3W, or 10 mg/kg Q2W) vs docetaxel (for previously treated NSCLC) or platinum- based chemo (for previously untreated NSCLC) Q3W. All studies included pts with stable brain metastases (ie, no symptoms or intracranial progression). Response (systemic, including in brain) was assessed per RECIST v1.1 by blinded, independent central review. Results: 3170 pts were included, 293 with and 2877 without baseline brain metastases; median (range) follow-up at data cutoff was 18.4 (0.5-43.7) mo and 12.6 (0.1-42.5) mo, respectively. HRs for OS and PFS were less than 1 with pembro vs chemo irrespective of baseline brain metastasis status (Table). Objective response rates were similar with pembro vs chemo but duration of response was longer with pembro. Fewer treatment- related AEs occurred with pembro vs chemo both in pts with brain metastases (66% vs 84%) and without (67% vs 88%); immune-mediated AEs and infusion reactions occurred in 21% vs 9%, respectively, with brain metastases and 25% vs 8% without. Conclusions: Pembro improved clinical outcomes and was well-tolerated vs chemo in pts with stable brain metastases, and provided similar outcomes in pts with and without brain metastases. Pembro is standard treatment in pts with advanced PD-L1-positive NSCLC, irrespective of brain metastases at baseline. (Table Presented) .