Chemotherapy-free regimen: Real-world efficacy and safety of anlotinib plus PD-1/PD-L1 inhibitors in advanced non-small cell lung cancer.

Objective: Chemotherapy-based regimens remain the standard first- and second-line treatment options for patients with driver gene-negative non-small cell lung cancer (NSCLC). However, in real-world settings, certain patients cannot tolerate chemotherapy or opt to decline it. Immune checkpoint inhibitors (ICIs) constitute the preferred chemotherapy-free alternative. To enhance patient prognosis, this study aimed to examine the efficacy of ICIs combined with anlotinib in real-world scenarios. Methods: This prospective, multicenter, real-world study evaluated the efficacy and safety of ICIs combined with anlotinib in patients with advanced NSCLC. Patients undergoing first- or second-line treatment were enrolled. The primary endpoint was progression-free survival (PFS), while the secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Results: In total, 242 patients were enrolled from 28 centers. The median PFS for the entire cohort was 7.8 [95% confidence interval (95% CI), 7.0-9.5] months, OS events occurred in 112 (46.3%) patients, with a current median OS of 17.0 (95% CI, 15.1-19.4) months. The ORR and DCR were 36.0% (95% CI, 30.2%-42.2%) and 97.9% (95% CI, 95.3%-99.1%), respectively. The median PFS was 9.8 (95% CI, 7.4-12.5) months for first-line therapy and 6.9 (95% CI, 6.0-8.3) months for second-line therapy. Treatment-related adverse events (AEs) occurred in 198 (81.8%) patients, with grade 3-4 AEs reported in 22 (9.1%) patients. Conclusions: This multicenter, real-world study demonstrates that the anlotinib-ICI combination regimen exhibits clinically meaningful efficacy and tolerability as a chemotherapy-free alternative for advanced NSCLC, offering viable evidence to guide treatment for patients who are unsuitable for conventional chemotherapy.