Organ-specific metastatic progression in non-small cell lung cancer treated with pembrolizumab versus atezolizumab: A TrinetX network analysis.

Abstract

11182 Background: Immune checkpoint inhibitors (ICIs) targeting the PD-1 (Pembrolizumab) and PD-L1 (Atezolizumab) have revolutionized the first-line management of metastatic non-small cell lung cancer (mNSCLC). While these agents are often considered clinically interchangeable, the differences in molecular binding mechanism and tissue-specific penetration may lead to distinct therapeutic patterns. Since the real-world evidence on the propensity for organ-specific metastatic spread remains limited, we aim to compare organ-specific metastatic progression patterns between the two therapies. Methods: We conducted a retrospective cohort study utilizing the TriNetX US Collaborative Network. After identifying adults with stage IV mNSCLC on initial Pembrolizumab or Atezolizumab monotherapy, patients with pre-existing metastases at the specific organ site of interest were excluded. Propensity score matching (1:1) was performed to balance cohorts across demographic and clinical variables. Our endpoints were metastases to the CNS, mediastinum, bone, liver, adrenal glands, and skin over 365 days. Hazard ratios (HR) were estimated using Cox proportional hazards models. Results: Atezolizumab was associated with a significantly higher risk of CNS metastases compared with Pembrolizumab (1-year incidence: 16.9% vs 6.1%; HR 3.08, 95%CI: 2.73-3.46; p < 0.001). A similar pattern was seen in the mediastinum (HR 1.62, 95% CI: 1.32–1.99), bone (HR 1.53, 95% CI: 1.38–1.70), liver (11.5% vs 7.8%; HR 1.55, 95% CI: 1.37–1.75), and adrenal glands (HR 1.43, 95% CI: 1.20–1.75). In contrast, an inverse relationship was observed in the skin where Atezolizumab showed a significantly lower risk of metastases (1.0% vs 1.7%; HR 0.59, 95% CI: 0.44 - 0.79; p = 0.01). Conclusions: Markedly distinct patterns of organ-specific metastasis were seen, where Atezolizumab consistently demonstrated an elevated risk of progression in the CNS and visceral organs, whereas Pembrolizumab showed a greater propensity for cutaneous progression. These observations indicate that the selection between PD-1 and PD-L1 inhibition may influence the location of the subsequent site of disease progression. Metastatic Site Atezolizumab Cohort (Events / N) Pembrolizumab Cohort (Events / N) Hazard Ratio* (95% CI) P-Value CNS 994 / 5,890 376 / 6,138 3.08 (2.73 – 3.46) <0.001 Mediastinum 228 / 7,043 150 / 7,153 1.62 (1.32 – 1.99) 0.02 Bone 824 / 4,997 624 / 5,374 1.53 (1.38 – 1.70) 0.43 Liver 602 / 5,250 490 / 6,262 1.55 (1.37 – 1.75) 0.35 Adrenal Gland 287 / 6,821 213 / 6,912 1.43 (1.20 – 1.75) 0.068 Skin 71 / 7,306 123 / 7,177 0.59 (0.44 – 0.79) 0.01 Note: N varies by organ site due to the exclusion of patients with pre-existing metastases at that specific site. *Hazard Ratio > 1.0 indicates increased risk with Atezolizumab; HR < 1.0 indicates increased risk with Pembrolizumab.