Efficacy and Safety of Treatment Beyond Progression with anti-PD-(L)1 Therapy in Patients with Advanced Non-Small Cell Lung Cancer: A Meta-analysis

Background The benefit of continuing anti-PD-(L)1 therapy beyond progression in advanced non-small cell lung cancer (NSCLC) remains unclear. This meta-analysis evaluates whether continued PD-(L)1 blockade offers survival advantage after progression on first-line therapy. Methods PubMed and Cochrane Library were searched through June 1, 2024. Major conference abstracts were also reviewed. Included studies involved patients with NSCLC who progressed after first-line anti-PD-(L)1 therapy. Exclusions included reviews, letters, non-clinical studies, and incomplete data. Two reviewers independently extracted data. Analysis was conducted on July 1, 2024. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and grade ≥ 3 adverse events. Comparative efficacy was analyzed using the onlinemeta v1.0 tool. Results A total of 15 studies (9 single-arm, 6 randomized) involving 2172 patients were included. PD-(L)1 inhibitor plus chemotherapy beyond progression showed the best ORR (28.8%, 95% CI − 22.0% to 36.6%) and longest median OS (16.29 months, 95% CI − 10.33 to 22.24). PD-(L)1 monotherapy had the lowest rate of severe adverse events (7.1%, 95% CI − 3.7% to 12.1%). Conclusions Continuing anti-PD-(L)1 therapy beyond progression, especially when combined with chemotherapy, may improve survival in advanced NSCLC, with acceptable safety. These findings offer insights for future clinical decision-making and trials.