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

This retrospective study used propensity-weighted analyses of longitudinal electronic health record data from 3,454 patients with advanced non-small cell lung cancer to compare the real-world effectiveness of second-line treatment options following disease progression on first-line therapy. Among patients who had previously received targeted therapy, continuing with a targeted approach in the second line was associated with a life expectancy advantage of more than two to three months over non-targeted or combination regimens. For patients who had progressed on first-line chemo-immunotherapy combinations, repeating a chemo-immunotherapy regimen in the second line outperformed chemotherapy alone, with survival advantages of nearly three to nearly six months depending on the timing of progression.

These findings fill an important gap in oncology evidence, as second-line treatment decisions for advanced lung cancer have historically received far less research attention than first-line care despite the poor prognosis that follows initial disease progression. The study demonstrates that real-world longitudinal data, when analyzed with rigorous statistical methods, can yield clinically meaningful guidance for treatment sequencing and underscores the urgent need for prospective validation of these findings to better inform care decisions for patients with advanced lung cancer.