Organ-metastatic landscape delineates overall and site-specific immune-related adverse events of PD-L1 blockade in advanced NSCLC.

It remains unknown whether metastases to different organs confer varying susceptibility to immune-related adverse events (irAEs) within a specific tumor type. We conducted a retrospective study included 708 advanced patients with non-small cell lung cancer (NSCLC) who received atezolizumab in two randomized controlled trials (OAK and POPLAR). Overall, irAEs were less frequent in patients with bone (OR = 0.52, p = 0.039) and pleural effusion metastases (OR = 0.65, p = 0.039), while more frequent in those with brain metastasis (OR = 1.96, p = 0.023). Cumulative irAEs risk differed significantly for patients with extra-thoracic (p = 0.034) but not intra-thoracic metastases (p = 0.680). In terms of site-specific irAEs, hepatitis, hypothyroidism, and rash were less frequent in patients with bone metastasis, whereas pneumonitis, adrenal insufficiency, and ocular inflammatory toxicity were more concentrated in patients with brain metastasis. A metastasis-based scoring system was developed by integrating the organ-metastatic landscape to identify high-risk populations for irAEs among NSCLC patients received PD-L1 blockade (p = 0.009). These findings highlight the predictive value of the organ-metastatic landscape for irAEs in advanced NSCLC received PD-L1 blockade.