Efficacy of continuing pembrolizumab after progression on first-line treatment in stage IV non-small cell lung cancer: a prospective real-world study

This prospective observational study investigated the efficacy of pembrolizumab administered as first-line therapy and the survival outcomes of continuing or combining it with other agents after disease progression in patients with stage IV non-small cell lung cancer (NSCLC). A total of 63 patients who experienced disease progression following pembrolizumab-based first-line treatment between February 2019 and July 2024 were prospectively enrolled. Patients were randomized into two cohorts based on treatment strategy: a treated beyond progression (TBP) group (n = 39) to receive continued pembrolizumab monotherapy or pembrolizumab-based combination regimens after disease progression, and a non-TBP (NTBP) group (n = 24), which discontinued pembrolizumab upon progression. The primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). The median PFS during first-line therapy (mPFS1) was 6.97 months. In the TBP group, the median PFS from first-line initiation to progression after second-line therapy (mPFS2) was 17.6 months, with an ORR of 20.5% and a DCR of 74.4%. OS in the TBP group was significantly longer than that in NTBP group (29.4 vs. 12.4 months, P < 0.001). Multivariate Cox regression analysis identified continued pembrolizumab use and favorable ECOG performance status as independent predictors of prolonged OS. These findings suggest that continued pembrolizumab use or combination therapy after disease progression significantly enhances survival benefits in advanced NSCLC, underscoring the importance of individualized treatment strategies based on clinical characteristics and treatment response.