Work

Real-World Effectiveness of Second-Line Therapies in Advanced Non-Small Cell Lung Cancer: Insights From Propensity-Weighted Comparative Analyses of Longitudinal EHR Data

Year: 2025

Type: article

Abstract: BACKGROUND: While substantial research has focused on first-line (1L) therapies for advanced-stage non-small cell lung cancer (aNSCLC), less is known about the effectiveness of second-line (2L) treatments following disease progression on 1L. The poor prognosis after 1L progression, limited guidance for 2L treatment, and constraints of clinical trials in addressing these questions underscore the need for real-world comparative effectiveness research. METHODS: We conducted a retrospective analysis to compare real-world overall survival (rwOS) associated with 2L treatments among patients with disease progression during 1L. Eligible patients were selected from Flatiron Health's nationwide electronic health record (EHR)-derived de-identified database. 1L and 2L treatments were categorized as chemotherapy-only (Chemo-alone), combination chemo- and immunotherapy (Chemo + Immuno), immunotherapy-only (IO-alone), targeted-alone therapy, or targeted-plus therapy. We used inverse probability of treatment weighting to adjust for extensive static and longitudinal patient-level confounding and compared rwOS using Kaplan-Meier curves and restricted mean survival time (RMST). RESULTS: Among patients previously treated with 1L Targeted therapy, those receiving 2L Targeted-alone therapy had longer life expectancies than those receiving a nontargeted (ΔRMST-36 + 2.61 months) or Targeted-plus regimen (ΔRMST-36 + 3.11 months). For patients progressing on 1L Chemo + Immuno, 2L Chemo + Immuno outperformed Chemo-alone (ΔRMST-36 + 2.98 months). Among patients progressing ≥1 year after initiating 1L IO-alone, 2L Chemo + Immuno again showed better life expectancy than Chemo-alone (ΔRMST-36 + 5.70 months). CONCLUSIONS: Longitudinal real-world data can enhance assessment of 2L therapy effectiveness. After confounder adjustment, we found clinically meaningful survival differences by 2L choice. These findings underscore the importance of 2L treatment selection and the need for prospective validation.

Source: Clinical Lung Cancer

DOI: 10.1016/j.cllc.2025.09.010

Authors: Gary C.N. Hettinger, Qi Long, Ravi B. Parikh

Institutions: New York University, University of Pennsylvania, Abramson Cancer Center, Emory University

Language: English

Topic: Lung Cancer Treatments and Mutations

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,200