Cemiplimab monotherapy as first-line (1L) treatment of patients with brain metastases from advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) ≥ 50%: EMPOWER-Lung 1 subgroup analysis.

Abstract

9085 Background: In the Phase 3, EMPOWER-Lung 1 study, cemiplimab monotherapy provided significant survival benefit and an acceptable safety profile vs chemotherapy in patients with advanced NSCLC and PD-L1 ≥50%. EMPOWER-Lung 1 included patients with brain metastases at baseline who are typically underrepresented in clinical trials. Other published exploratory analyses in single-cohort studies suggest benefit from immunotherapy in this patient population. Here, we present subgroup analysis of patients with brain metastasis from EMPOWER-Lung 1. Methods: Patients were randomized 1:1 to cemiplimab 350 mg IV every 3 weeks or investigator’s choice of chemotherapy (NCT03088540). Patients with treated, clinically stable brain metastases (radiological stability not required) were eligible to enroll and are the focus of this subgroup analysis from the PD-L1 ≥50% population (n=563) of the EMPOWER-Lung 1 study. Results: A total of 68 of 563 (12.1%) cases had treated stable brain metastases at time of randomization. Patients were evenly distributed between cemiplimab (n=34) and chemotherapy (n=34), with similar median duration of follow-up (Table). Baseline characteristics were generally similar; median (range) age: 60.0 (45–76 ) vs 62.0 (48–77); male: 97.1% vs 85.3%; and non-squamous histology: 85.3% vs 76.5%; between cemiplimab vs chemotherapy, respectively. Per independent review committee, median overall survival (OS, 18.7 vs 11.7 months), median progression-free survival (PFS, 10.4 vs 5.3 months), and objective response rate (ORR, 41.2% vs 8.8%) were superior with cemiplimab vs chemotherapy (Table). After baseline, central nervous system (CNS) disease progression occurred in 2 (5.9%) patients with cemiplimab vs 4 (11.8%) patients with chemotherapy; extra-CNS disease progression occurred in 9 (26.5%) patients with cemiplimab vs 15 (44.1%) patients with chemotherapy. Conclusions: 1L cemiplimab monotherapy improved OS, PFS, and ORR vs chemotherapy, in patients with advanced NSCLC with PD-L1 ≥50%, and clinically stable brain metastases at baseline. Cemiplimab monotherapy represents a suitable option for this subgroup of patients. Clinical trial information: NCT03088540. [Table: see text]

PD-1/PD-L1 Inhibitors as Monotherapy in the First-Line Treatment of Advanced Non-Small Cell Lung Cancer Patients with High PD-L1 Expression: An Expert Position Statement

“…OS was significantly higher with CEMI than with chemotherapy in patients with brain metastases (median follow-up 33.3 months, HR = 0.42, 95% CI [0.20, 0.87]) [27]. The ORR was also improved with CEMI (41.2%, 95% CI [24.6, 59.3]) versus chemotherapy (8.8%, 95% CI [1.9, 23.7]) [29]. However, although OS with PEMBRO was numerically superior to chemotherapy, it did not reach statistical significance [20] (Table 5).…”

Immunotherapy in non-small cell lung cancer: Past, present, and future directions

“…Cemiplimab monotherapy was examined in patients with PD-L1 ≥ 50% in a subgroup analysis of the EMPOWER-Lung 1 trial. This trial showed improved PFS (10.4 months vs 5.3 months, HR 0.45, 0.22-0.92, p=0.0231) and OS (18.7 months vs 11.7 months, HR 0.17, 0.04-0.76, p=0.0091) compared to chemotherapy alone in patients with treated, clinically stable brain metastases ( 79 ). To further study CNS disease, the ATEZO-BRAIN study was a phase II trial of atezolizumab with carboplatin and pemetrexed in patient with metastatic nonsquamous NSCLC and untreated brain metastases.…”

“…A subsequent study of atezolizumab compared to chemotherapy demonstrated similar efficacy in metastatic NSCLC with PD-L1 expression ≥50% or immune cell (IC) PD-L1 ≥10% (median OS 20.2 months versus 13.1 months, HR 0.59, p=0.01) ( 66 ). Cemiplimab is the newest PD-1 inhibitor approved in this setting, demonstrating improvements in PFS (8.2 months vs 5.7 months, HR 0.54, 0.43-0.68, p<0.0001) and OS (median NR vs 14.2 months, HR 0.57, 0.42-0.77, p=0.0002) compared to chemotherapy in PD-L1≥50% disease ( 79 ). The similarities in efficacy across different trials suggest that this is a class effect of PD-1/PD-L1 inhibitors.…”

Safety and efficacy of immune checkpoint blockade in patients with advanced nonsmall cell lung cancer and brain metastasis

“…A post hoc exploratory analysis reported a reduced risk of IC PFS and death by 72%, as well as an IC disease progression benefit in favour of cemiplimab. In particular, IC disease progression occurred in 2/34 (5.9%) of cemiplimab‐treated patients compared to 4/34 (11.8%) chemotherapy‐treated patients 83 …”

“…In particular, IC disease progression occurred in 2/34 (5.9%) of cemiplimab-treated patients compared to 4/34 (11.8%) chemotherapy-treated patients. 83 The EMPOWER-Lung 3 trial included 31 out of 466 (6.7%) patients with stable brain metastatic disease. 24/312 patients (7.7) received the combination of cemiplimab and chemotherapy, whereas 7/154 patients (4.5) were randomised into the chemotherapy plus placebo group.…”