Real-World Outcomes and Prognostic Factors Among Patients with Advanced Non-Small Cell Lung Cancer and High PD-L1 Expression Treated with Immune Checkpoint Inhibitors as First-Line Therapy

Wenzhen Ge,1 Ning Wu,1 Jessica J Jalbert,1 Ruben GW Quek,1 Jinjie Liu,2 Petra Rietschel,1 Jean-Francois Pouliot,1 James Harnett,1 Melinda Laine Hsu,3 Josephine L Feliciano4 1Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA; 2Genesis Research, LLC, Hoboken, NJ, USA; 3University Hospitals, Cleveland Medical Center, Cleveland, OH, USA; 4Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USACorrespondence: Josephine L Feliciano, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA, Tel +1 410 550 1711, Email jfelici4@jhmi.eduBackground: Immune checkpoint inhibitors (ICIs) are standard-of-care for patients with advanced non-small cell lung cancer (aNSCLC) and programmed cell death-ligand 1 (PD-L1) expression ≥ 50%.Methods: A retrospective cohort study was conducted using the US de-identified electronic health record-derived Flatiron Health aNSCLC database (January 1, 2018, to July 31, 2021) among patients with PD-L1 ≥ 50% initiating first-line ICIs with or without chemotherapy. A clinical trial-like sub-cohort was also identified with Eastern Cooperative Oncology Group performance status 0– 1, adequate organ function, and no brain metastases or other primary cancers. Kaplan–Meier methods were used to estimate time to treatment discontinuation, time to next treatment, progression-free survival and overall survival (OS) by ICI regimen (ICI+chemotherapy, ICI monotherapy) and PD-L1 expression (50– 69%, 70– 89%, 90– 100%). Cox proportional hazard models were used to examine associations between ICI regimen, PD-L1 level, and OS, adjusting for baseline demographic and clinical variables.Results: A total of 2631 patients with aNSCLC initiating ICI+chemotherapy (n = 992) or ICI monotherapy (n = 1639) were included; median (Q1, Q3) age was 71 (63– 78) years and 51.6% were male. The trial-like sub-cohort (n = 1029) generally had better outcomes vs. the overall cohort. Patients receiving ICI+chemotherapy generally had longer median OS vs. ICI monotherapy. Multivariable analyses showed no association between ICI regimen and OS among patients with PD-L1 70– 89% (hazard ratio [HR]: 0.90, 95% confidence interval [CI]: 0.73– 1.09) or 90– 100% (HR: 0.91, 95% CI: 0.77– 1.08), but patients with PD-L1 50– 69% receiving ICI+chemotherapy had longer OS (HR: 0.80, 95% CI: 0.64– 0.99).Conclusion: Outcomes in real-world clinical trial-like patients with aNSCLC approached those reported in pivotal ICI trials in high PD-L1 expressers. ICI monotherapy offers a potential alternative in patients with PD-L1 ≥ 70% while avoiding potential chemotherapy toxicity exposure; the benefits are less clear in patients with PD-L1 50– 69%. Future studies should confirm these findings.Keywords: immune checkpoint inhibitors, non-small cell lung cancer, PD-L1 expression, real-world data, overall survival, progression-free survival