Pembrolizumab as First-Line Palliative Therapy in PD-L1 Overexpressing (≥ 50%) NSCLC: Real-world Results with Special Focus on PS ≥ 2, Brain Metastases, and Steroids

Approximately every second patient from everyday clinical practice receives pembrolizumab as first-line palliative treatment without clear evidence from clinical trials. Analyzing 153 consecutive patients, a comorbidity-defined PS >= 2, symptomatic brain metastases, or baseline steroids were associated with substantially reduced survival. All-in-all, real-world and clinical trial efficacy correspond well as long as baseline characteristics of real world and study patients match. Introduction: Pembrolizumab is a highly effective standard of care in PD-L1 overexpressing (>= 50%) non-small-cell lung cancer. However, a substantial share of patients from everyday clinical practice is treated without clear evidence from clinical trials. Patients and Methods: We performed a retrospective multicentric study including all consecutive patients from 6 certified lung cancer centers in Berlin, Germany, having received pembrolizumab as first-line palliative therapy from January 1 until December 31, 2017. Aims were to validate published clinical trials with a special focus on efficacy and outcome in patients with reduced performance status (PS), brain metastases, and steroids. Results: A total of 153 patients were included (median age 69 years, 58% men, 69% adenocarcinoma). Rates for PS >= 2, brain metastases, and steroids were 24.8%, 20.9%, and 24.2%, respectively. Median objective response rate, progression-free and overall survival were 48.5%, 8.2 and 22.0 months for all patients and 52.4%, 8.8 and 29.2 months in patients fulfilling the inclusion criteria for the KEYNOTE-024 trial. Patients with a comorbidity-defined PS >= 2, symptomatic brain metastases requiring upfront radiotherapy, or baseline steroids had significantly reduced survival. In contrast, durable responses occurred with a tumor-related PS >= 2 or asymptomatic brain metastases. Grade 3/4 and 5 immunerelated adverse events affected 13.7% and 2.0% of patients. Conclusion: Real-world and clinical trial efficacy with upfront pembrolizumab correspond well. Pembrolizumab may sufficiently control asymptomatic brain metastases and may improve a cancer-related reduced PS. However, the frail share of patients with a comorbidity-defined PS >= 2, symptomatic brain metastases, or baseline steroids derives no relevant benefit. (C) 2021 Elsevier Inc. All rights reserved.